Compact star

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Compact_star

In astronomy, the term compact star (or compact object) refers collectively to white dwarfs, neutron stars, and black holes. It would grow to include exotic stars if such hypothetical, dense bodies are confirmed to exist. All compact objects have a high mass relative to their radius, giving them a very high density, compared to ordinary atomic matter.

Compact stars are often the endpoints of stellar evolution and, in this respect, are also called stellar remnants. The state and type of a stellar remnant depends primarily on the mass of the star that it formed from. The ambiguous term compact star is often used when the exact nature of the star is not known, but evidence suggests that it has a very small radius compared to ordinary stars. A compact star that is not a black hole may be called a degenerate star.

In June 2020, astronomers reported narrowing down the source of Fast Radio Bursts (FRBs), which may now plausibly include "compact-object mergers and magnetars arising from normal core collapse supernovae".

Formation

The usual endpoint of stellar evolution is the formation of a compact star.

All active stars will eventually come to a point in their evolution when the outward radiation pressure from the nuclear fusions in its interior can no longer resist the ever-present gravitational forces. When this happens, the star collapses under its own weight and undergoes the process of stellar death. For most stars, this will result in the formation of a very dense and compact stellar remnant, also known as a compact star.

Compact stars have no internal energy production, but will—with the exception of black holes—usually radiate for millions of years with excess heat left from the collapse itself.

According to the most recent understanding, compact stars could also form during the phase separations of the early Universe following the Big Bang. Primordial origins of known compact objects have not been determined with certainty.

Lifetime

Although compact stars may radiate, and thus cool off and lose energy, they do not depend on high temperatures to maintain their structure, as ordinary stars do. Barring external disturbances and proton decay, they can persist virtually forever. Black holes are however generally believed to finally evaporate from Hawking radiation after trillions of years. According to our current standard models of physical cosmology, all stars will eventually evolve into cool and dark compact stars, by the time the Universe enters the so-called degenerate era in a very distant future.

The somewhat wider definition of compact objects often includes smaller solid objects such as planets, asteroids, and comets. There are a remarkable variety of stars and other clumps of hot matter, but all matter in the Universe must eventually end as some form of compact stellar or substellar object, according to current theoretical interpretations of thermodynamics.

White dwarfs

Main article: White dwarf

 

The Eskimo Nebula is illuminated by a white dwarf at its center.

The stars called white or degenerate dwarfs are made up mainly of degenerate matter; typically carbon and oxygen nuclei in a sea of degenerate electrons. White dwarfs arise from the cores of main-sequence stars and are therefore very hot when they are formed. As they cool they will redden and dim until they eventually become dark black dwarfs. White dwarfs were observed in the 19th century, but the extremely high densities and pressures they contain were not explained until the 1920s.

The equation of state for degenerate matter is "soft", meaning that adding more mass will result in a smaller object. Continuing to add mass to what begins as a white dwarf, the object shrinks and the central density becomes even greater, with higher degenerate-electron energies. After the degenerate star's mass has grown sufficiently that its radius has shrunk to only a few thousand kilometers, the mass will be approaching the Chandrasekhar limit – the theoretical upper limit of the mass of a white dwarf, about 1.4 times the mass of the Sun (M_☉).

If matter were removed from the center of a white dwarf and slowly compressed, electrons would first be forced to combine with nuclei, changing their protons to neutrons by inverse beta decay. The equilibrium would shift towards heavier, neutron-richer nuclei that are not stable at everyday densities. As the density increases, these nuclei become still larger and less well-bound. At a critical density of about 4×10¹⁴ kg/m³ – called the “neutron drip line” – the atomic nucleus would tend to dissolve into unbound protons and neutrons. If further compressed, eventually it would reach a point where the matter is on the order of the density of an atomic nucleus – about 2×10¹⁷ kg/m³. At that density the matter would be chiefly free neutrons, with a light scattering of protons and electrons.

Neutron stars

Main article: Neutron star

 

The Crab Nebula is a supernova remnant containing the Crab Pulsar, a neutron star.

In certain binary stars containing a white dwarf, mass is transferred from the companion star onto the white dwarf, eventually pushing it over the Chandrasekhar limit. Electrons react with protons to form neutrons and thus no longer supply the necessary pressure to resist gravity, causing the star to collapse. If the center of the star is composed mostly of carbon and oxygen then such a gravitational collapse will ignite runaway fusion of the carbon and oxygen, resulting in a Type Ia supernova that entirely blows apart the star before the collapse can become irreversible. If the center is composed mostly of magnesium or heavier elements, the collapse continues. As the density further increases, the remaining electrons react with the protons to form more neutrons. The collapse continues until (at higher density) the neutrons become degenerate. A new equilibrium is possible after the star shrinks by three orders of magnitude, to a radius between 10 and 20 km. This is a neutron star.

Although the first neutron star was not observed until 1967 when the first radio pulsar was discovered, neutron stars were proposed by Baade and Zwicky in 1933, only one year after the neutron was discovered in 1932. They realized that because neutron stars are so dense, the collapse of an ordinary star to a neutron star would liberate a large amount of gravitational potential energy, providing a possible explanation for supernovae. This is the explanation for supernovae of types Ib, Ic, and II. Such supernovae occur when the iron core of a massive star exceeds the Chandrasekhar limit and collapses to a neutron star.

Like electrons, neutrons are fermions. They therefore provide neutron degeneracy pressure to support a neutron star against collapse. In addition, repulsive neutron-neutron interactions provide additional pressure. Like the Chandrasekhar limit for white dwarfs, there is a limiting mass for neutron stars: the Tolman–Oppenheimer–Volkoff limit, where these forces are no longer sufficient to hold up the star. As the forces in dense hadronic matter are not well understood, this limit is not known exactly but is thought to be between 2 and 3 M_☉. If more mass accretes onto a neutron star, eventually this mass limit will be reached. What happens next is not completely clear.

Black holes

Main articles: Black hole and Stellar black hole

 

A simulated black hole of ten solar masses, at a distance of 600 km

As more mass is accumulated, equilibrium against gravitational collapse exceeds its breaking point. Once the star's pressure is insufficient to counterbalance gravity, a catastrophic gravitational collapse occurs within milliseconds. The escape velocity at the surface, already at least 1⁄3 light speed, quickly reaches the velocity of light. At that point no energy or matter can escape and a black hole has formed. Because all light and matter is trapped within an event horizon, a black hole appears truly black, except for the possibility of very faint Hawking radiation. It is presumed that the collapse will continue inside the event horizon.

In the classical theory of general relativity, a gravitational singularity occupying no more than a point will form. There may be a new halt of the catastrophic gravitational collapse at a size comparable to the Planck length, but at these lengths there is no known theory of gravity to predict what will happen. Adding any extra mass to the black hole will cause the radius of the event horizon to increase linearly with the mass of the central singularity. This will induce certain changes in the properties of the black hole, such as reducing the tidal stress near the event horizon, and reducing the gravitational field strength at the horizon. However, there will not be any further qualitative changes in the structure associated with any mass increase.

Alternative black hole models

• Fuzzball
• Gravastar
• Dark-energy star
• Black star
• Magnetospheric eternally collapsing object
• Dark star
• Primordial black holes

Exotic stars

Main article: Exotic star

An exotic star is a hypothetical compact star composed of something other than electrons, protons, and neutrons balanced against gravitational collapse by degeneracy pressure or other quantum properties. These include strange stars (composed of strange matter) and the more speculative preon stars (composed of preons).

Exotic stars are hypothetical, but observations released by the Chandra X-Ray Observatory on April 10, 2002 detected two candidate strange stars, designated RX J1856.5-3754 and 3C58, which had previously been thought to be neutron stars. Based on the known laws of physics, the former appeared much smaller and the latter much colder than they should, suggesting that they are composed of material denser than neutronium. However, these observations are met with skepticism by researchers who say the results were not conclusive.

Quark stars and strange stars

Main article: Quark star

If neutrons are squeezed enough at a high temperature, they will decompose into their component quarks, forming what is known as a quark matter. In this case, the star will shrink further and become denser, but instead of a total collapse into a black hole, it is possible that the star may stabilize itself and survive in this state indefinitely, so long as no more mass is added. It has, to an extent, become a very large nucleon. A star in this hypothetical state is called a "quark star" or more specifically a "strange star". The pulsar 3C58 has been suggested as a possible quark star. Most neutron stars are thought to hold a core of quark matter but this has proven difficult to determine observationally.

Preon stars

A preon star is a proposed type of compact star made of preons, a group of hypothetical subatomic particles. Preon stars would be expected to have huge densities, exceeding 10²³ kilogram per cubic meter – intermediate between quark stars and black holes. Preon stars could originate from supernova explosions or the Big Bang; however, current observations from particle accelerators speak against the existence of preons.

Q stars

Main article: Q star

Q stars are hypothetical compact, heavier neutron stars with an exotic state of matter where particle numbers are preserved with radii less than 1.5 times the corresponding Schwarzschild radius. Q stars are also called "gray holes".

Electroweak stars

Main article: Electroweak star

An electroweak star is a theoretical type of exotic star, whereby the gravitational collapse of the star is prevented by radiation pressure resulting from electroweak burning, that is, the energy released by conversion of quarks to leptons through the electroweak force. This process occurs in a volume at the star's core approximately the size of an apple, containing about two Earth masses.

Boson star

A boson star is a hypothetical astronomical object that is formed out of particles called bosons (conventional stars are formed out of fermions). For this type of star to exist, there must be a stable type of boson with repulsive self-interaction. As of 2016 there is no significant evidence that such a star exists. However, it may become possible to detect them by the gravitational radiation emitted by a pair of co-orbiting boson stars.

Compact relativistic objects and the generalized uncertainty principle

Based on the generalized uncertainty principle (GUP), proposed by some approaches to quantum gravity such as string theory and doubly special relativity, the effect of GUP on the thermodynamic properties of compact stars with two different components has been studied recently. Tawfik et al. noted that the existence of quantum gravity correction tends to resist the collapse of stars if the GUP parameter is taking values between Planck scale and electroweak scale. Comparing with other approaches, it was found that the radii of compact stars should be smaller and increasing energy decreases the radii of the compact stars.

Neutronium

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Neutronium

Neutronium (sometimes shortened to neutrium, also referred to as neutrite) is a hypothetical substance composed purely of neutrons. The word was coined by scientist Andreas von Antropoff in 1926 (before the 1932 discovery of the neutron) for the hypothetical "element of atomic number zero" (with zero protons in its nucleus) that he placed at the head of the periodic table (denoted by -, or Nu). However, the meaning of the term has changed over time, and from the last half of the 20th century onward it has been also used to refer to extremely dense substances resembling the neutron-degenerate matter theorized to exist in the cores of neutron stars; hereinafter "degenerate neutronium" will refer to this.

In neutron stars

Main article: Neutron star

Neutronium is used in popular physics literature to refer to the material present in the cores of neutron stars (stars which are too massive to be supported by electron degeneracy pressure and which collapse into a denser phase of matter). This term is very rarely used in scientific literature, for three reasons: there are multiple definitions for the term "neutronium"; there is considerable uncertainty over the composition of the material in the cores of neutron stars (it could be neutron-degenerate matter, strange matter, quark matter, or a variant or combination of the above); the properties of neutron star material should depend on depth due to changing pressure (see below), and no sharp boundary between the crust (consisting primarily of atomic nuclei) and almost protonless inner layer is expected to exist.

When neutron star core material is presumed to consist mostly of free neutrons, it is typically referred to as neutron-degenerate matter in scientific literature.

In the periodic table

The term "neutronium" was coined in 1926 by Andreas von Antropoff for a conjectured form of matter made up of neutrons with no protons or electrons, which he placed as the chemical element of atomic number zero at the head of his new version of the periodic table. It was subsequently placed in the middle of several spiral representations of the periodic system for classifying the chemical elements, such as those of Charles Janet (1928), E. I. Emerson (1944), and John D. Clark (1950).

Although the term is not used in the scientific literature either for a condensed form of matter, or as an element, there have been reports that, besides the free neutron, there may exist two bound forms of neutrons without protons. If neutronium were considered to be an element, then these neutron clusters could be considered to be the isotopes of that element. However, these reports have not been further substantiated.

• Mononeutron: An isolated neutron undergoes beta decay with a mean lifetime of approximately 15 minutes (half-life of approximately 10 minutes), becoming a proton (the nucleus of hydrogen), an electron, and an antineutrino.
• Dineutron: The dineutron, containing two neutrons, was unambiguously observed in 2012 in the decay of beryllium-16. It is not a bound particle, but had been proposed as an extremely short-lived resonance state produced by nuclear reactions involving tritium. It has been suggested to have a transitory existence in nuclear reactions produced by helions (completely ionized helium-3 nuclei) that result in the formation of a proton and a nucleus having the same atomic number as the target nucleus but a mass number two units greater. The dineutron hypothesis had been used in nuclear reactions with exotic nuclei for a long time. Several applications of the dineutron in nuclear reactions can be found in review papers. Its existence has been proven to be relevant for nuclear structure of exotic nuclei. A system made up of only two neutrons is not bound, though the attraction between them is very nearly enough to make them so. This has some consequences on nucleosynthesis and the abundance of the chemical elements.
• Trineutron: A trineutron state consisting of three bound neutrons has not been detected, and is not expected to exist even for a short time.
• Tetraneutron: A tetraneutron is a hypothetical particle consisting of four bound neutrons. Reports of its existence have not been replicated.
• Pentaneutron: Calculations indicate that the hypothetical pentaneutron state, consisting of a cluster of five neutrons, would not be bound.

Although not called "neutronium", the National Nuclear Data Center's Nuclear Wallet Cards lists as its first "isotope" an "element" with the symbol n and atomic number Z = 0 and mass number A = 1. This "isotope" is described as decaying to hydrogen-1 with a half life of 10.24±0.2 min.

Properties

See also: Neutron star § Properties

Neutron matter is equivalent to a chemical element with atomic number 0, which is to say that it is equivalent to a species of atoms having no protons in their atomic nuclei. It is extremely radioactive; its only legitimate equivalent isotope, the free neutron, has a half-life of 10 minutes, which is approximately half that of the most stable known isotope of francium. Neutron matter decays quickly into hydrogen. Neutron matter has no electronic structure on account of its total lack of electrons.

While this lifetime is long enough to permit the study of neutronium's chemical properties, there are serious practical problems. Having no charge or electrons, neutronium would not interact strongly with ordinary low-energy photons (visible light) and would feel no electrostatic forces, so it would diffuse into the walls of most containers made of ordinary matter. Certain materials are able to resist diffusion or absorption of ultracold neutrons due to nuclear-quantum effects, specifically reflection caused by the strong interaction. At ambient temperature and in the presence of other elements, thermal neutrons readily undergo neutron capture to form heavier (and often radioactive) isotopes of that element.

Neutron matter at standard pressure and temperature is predicted by the ideal gas law to be less dense than even hydrogen, with a density of only 0.045 kg/m³ (roughly 27 times less dense than air and half as dense as hydrogen gas). Neutron matter is expected to remain gaseous down to absolute zero at normal pressures, as the zero-point energy of the system is too high to allow condensation. However, neutron matter should in theory form a degenerate gaseous superfluid at these temperatures, composed of transient neutron-pairs called dineutrons. Under extremely low pressure, this low temperature, gaseous superfluid should exhibit quantum coherence producing a Bose–Einstein condensate. At higher temperatures, neutron matter will only condense with sufficient pressure, and solidify with even greater pressure. Such pressures exist in neutron stars, where the extreme pressure causes the neutron matter to become degenerate. However, in the presence of atomic matter compressed to the state of electron degeneracy, β⁻ decay may be inhibited due to the Pauli exclusion principle, thus making free neutrons stable. Also, elevated pressures should make neutrons degenerate themselves.

Compared to ordinary elements, neutronium should be more compressible due to the absence of electrically charged protons and electrons. This makes neutronium more energetically favorable than (positive-Z) atomic nuclei and leads to their conversion to (degenerate) neutronium through electron capture, a process that is believed to occur in stellar cores in the final seconds of the lifetime of massive stars, where it is facilitated by cooling via
ν
_e emission. As a result, degenerate neutronium can have a density of 4×10¹⁷ kg/m³, roughly 14 orders of magnitude denser than the densest known ordinary substances. It was theorized that extreme pressures of order 100 MeV/fm³ (1.6×10³⁴ Pa) might deform the neutrons into a cubic symmetry, allowing tighter packing of neutrons, or cause a strange matter formation.

Deming regression

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Deming_regression 

 

Deming regression. The red lines show the error in both x and y. This is different from the traditional least squares method which measures error parallel to the y axis. The case shown, with deviations measured perpendicularly, arises when errors in x and y have equal variances.

In statistics, Deming regression, named after W. Edwards Deming, is an errors-in-variables model which tries to find the line of best fit for a two-dimensional dataset. It differs from the simple linear regression in that it accounts for errors in observations on both the x- and the y- axis. It is a special case of total least squares, which allows for any number of predictors and a more complicated error structure.

Deming regression is equivalent to the maximum likelihood estimation of an errors-in-variables model in which the errors for the two variables are assumed to be independent and normally distributed, and the ratio of their variances, denoted δ, is known. In practice, this ratio might be estimated from related data-sources; however the regression procedure takes no account for possible errors in estimating this ratio.

The Deming regression is only slightly more difficult to compute than the simple linear regression. Most statistical software packages used in clinical chemistry offer Deming regression.

The model was originally introduced by Adcock (1878) who considered the case δ = 1, and then more generally by Kummell (1879) with arbitrary δ. However their ideas remained largely unnoticed for more than 50 years, until they were revived by Koopmans (1936) and later propagated even more by Deming (1943). The latter book became so popular in clinical chemistry and related fields that the method was even dubbed Deming regression in those fields.

Specification

Assume that the available data (y_i, x_i) are measured observations of the "true" values (y_i*, x_i*), which lie on the regression line:

${\displaystyle \begin{array}{rl}{y}_i& =y_i^{\ast }+{\epsilon }_i,\\ x_i& =x_i^{\ast }+{\eta }_i,\end{array}}$

where errors ε and η are independent and the ratio of their variances is assumed to be known:

${\displaystyle \delta =\frac{{\sigma }_{\epsilon }^2}{{\sigma }_{\eta }^2}.}$

In practice, the variances of the ${\displaystyle x}$ and ${\displaystyle y}$ parameters are often unknown, which complicates the estimate of ${\displaystyle \delta }$. Note that when the measurement method for ${\displaystyle x}$ and ${\displaystyle y}$ is the same, these variances are likely to be equal, so ${\displaystyle \delta =1}$ for this case.

We seek to find the line of "best fit"

${\displaystyle y^{\ast }={\beta }_0+{\beta }_1{x}^{\ast },}$

such that the weighted sum of squared residuals of the model is minimized:

${\displaystyle SSR=\sum _{i=1}^n(\frac{{\epsilon }_i^2}{{\sigma }_{\epsilon }^2}+\frac{{\eta }_i^2}{{\sigma }_{\eta }^2})=\frac{1}{{\sigma }_{\epsilon }^2}\sum _{i=1}^n((y_i-{\beta }_0-{\beta }_1{x}_i^{\ast }{)}^2+\delta (x_i-x_i^{\ast }{)}^2)\to \underset{{\beta }_0,{\beta }_1,x_1^{\ast },\dots ,x_n^{\ast }}{min}SSR}$

See Jensen (2007) for a full derivation.

Solution

The solution can be expressed in terms of the second-degree sample moments. That is, we first calculate the following quantities (all sums go from i = 1 to n):

${\displaystyle \begin{array}{rl}& \overline{x}=\frac{1}{n}\sum x_i,\overline{y}=\frac{1}{n}\sum y_i,\\ & s_{xx}=\frac{1}{n}\sum (x_i-\overline{x}{)}^2,\\ & s_{xy}=\frac{1}{n}\sum (x_i-\overline{x})(y_i-\overline{y}),\\ & s_{yy}=\frac{1}{n}\sum (y_i-\overline{y}{)}^2.\end{array}}$

Finally, the least-squares estimates of model's parameters will be

${\displaystyle \begin{array}{rl}& {\hat{\beta }}_1=\frac{s_{yy}-\delta s_{xx}+\sqrt{(s_{yy}-\delta s_{xx}{)}^2+4\delta s_{xy}^2}}{2s_{xy}},\\ & {\hat{\beta }}_0=\overline{y}-{\hat{\beta }}_1\overline{x},\\ & {\hat{x}}_i^{\ast }=x_i+\frac{{\hat{\beta }}_1}{{\hat{\beta }}_1^2+\delta }(y_i-{\hat{\beta }}_0-{\hat{\beta }}_1{x}_i).\end{array}}$

Orthogonal regression

For the case of equal error variances, i.e., when ${\displaystyle \delta =1}$, Deming regression becomes orthogonal regression: it minimizes the sum of squared perpendicular distances from the data points to the regression line. In this case, denote each observation as a point z_j in the complex plane (i.e., the point (x_j, y_j) is written as z_j = x_j + iy_j where i is the imaginary unit). Denote as Z the sum of the squared differences of the data points from the centroid (also denoted in complex coordinates), which is the point whose horizontal and vertical locations are the averages of those of the data points. Then:

• If Z = 0, then every line through the centroid is a line of best orthogonal fit.
• If Z ≠ 0, the orthogonal regression line goes through the centroid and is parallel to the vector from the origin to ${\displaystyle \sqrt{Z}}$.

A trigonometric representation of the orthogonal regression line was given by Coolidge in 1913.

Application

In the case of three non-collinear points in the plane, the triangle with these points as its vertices has a unique Steiner inellipse that is tangent to the triangle's sides at their midpoints. The major axis of this ellipse falls on the orthogonal regression line for the three vertices. The quantification of a biological cell's intrinsic cellular noise can be quantified upon applying Deming regression to the observed behavior of a two reporter synthetic biological circuit.

York regression

The York regression extends Deming regression by allowing correlated errors in x and y.

Hypothalamic–pituitary–adrenal axis

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Hypothalamic%E2%80%93pituitary%E2%80%93adrenal_axis

 

Schematic of the HPA axis (CRH, corticotropin-releasing hormone; ACTH, adrenocorticotropic hormone)

 

Hypothalamus, pituitary gland and adrenal cortex

The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three components: the hypothalamus (a part of the brain located below the thalamus), the pituitary gland (a pea-shaped structure located below the hypothalamus), and the adrenal (also called "suprarenal") glands (small, conical organs on top of the kidneys). These organs and their interactions constitute the HPA axis.

The HPA axis is a major neuroendocrine system that controls reactions to stress and regulates many body processes, including digestion, the immune system, mood and emotions, sexuality, and energy storage and expenditure. It is the common mechanism for interactions among glands, hormones, and parts of the midbrain that mediate the general adaptation syndrome (GAS).

While steroid hormones are produced mainly in vertebrates, the physiological role of the HPA axis and corticosteroids in stress response is so fundamental that analogous systems can be found in invertebrates and monocellular organisms as well.

The HPA axis, hypothalamic–pituitary–gonadal axis (HPG), hypothalamic–pituitary–thyroid axis (HPT), and the hypothalamic–neurohypophyseal system are the four major neuroendocrine systems through which the hypothalamus and pituitary direct neuroendocrine function.

Anatomy

The key elements of the HPA axis are:

• The paraventricular nucleus of the hypothalamus, which contains neuroendocrine neurons which synthesize and secrete vasopressin and corticotropin-releasing hormone (CRH). These two peptides regulate:
  • The anterior lobe of the pituitary gland. In particular, CRH and vasopressin stimulate the secretion of adrenocorticotropic hormone (ACTH), once known as corticotropin. ACTH in turn acts on:
  • the adrenal cortex, which produces glucocorticoid hormones (mainly cortisol in humans) in response to stimulation by ACTH. Glucocorticoids in turn act back on the hypothalamus and pituitary (to suppress CRH and ACTH production) in a negative feedback cycle.

CRH and vasopressin are released from neurosecretory nerve terminals at the median eminence. CRH is transported to the anterior pituitary through the portal blood vessel system of the hypophyseal stalk and vasopressin is transported by axonal transport to the posterior pituitary gland. There, CRH and vasopressin act synergistically to stimulate the secretion of stored ACTH from corticotrope cells. ACTH is transported by the blood to the adrenal cortex of the adrenal gland, where it rapidly stimulates biosynthesis of corticosteroids such as cortisol from cholesterol. Cortisol is a major stress hormone and has effects on many tissues in the body, including the brain. In the brain, cortisol acts on two types of receptor – mineralocorticoid receptors and glucocorticoid receptors, and these are expressed by many different types of neurons. One important target of glucocorticoids is the hypothalamus, which is a major controlling centre of the HPA axis.

Vasopressin can be thought of as "water conservation hormone" and is also known as "antidiuretic hormone". It is released when the body is dehydrated and has potent water-conserving effects on the kidney. It is also a potent vasoconstrictor.

Important to the function of the HPA axis are some of the feedback loops:

• Cortisol produced in the adrenal cortex will negatively feedback to inhibit both the hypothalamus and the pituitary gland. This reduces the secretion of CRH and vasopressin, and also directly reduces the cleavage of proopiomelanocortin (POMC) into ACTH and β-endorphins.
• Epinephrine and norepinephrine (E/NE) are produced by the adrenal medulla through sympathetic stimulation and the local effects of cortisol (upregulation enzymes to make E/NE). E/NE will positively feedback to the pituitary and increase the breakdown of POMCs into ACTH and β-endorphins.

Function

Release of corticotropin-releasing hormone (CRH) from the hypothalamus is influenced by stress, physical activity, illness, by blood levels of cortisol and by the sleep/wake cycle (circadian rhythm). In healthy individuals, cortisol rises rapidly after wakening, reaching a peak within 30–45 minutes. It then gradually falls over the day, rising again in late afternoon. Cortisol levels then fall in late evening, reaching a trough during the middle of the night. This corresponds to the rest-activity cycle of the organism. An abnormally flattened circadian cortisol cycle has been linked with chronic fatigue syndrome, insomnia and burnout.

The HPA axis has a central role in regulating many homeostatic systems in the body, including the metabolic system, cardiovascular system, immune system, reproductive system and central nervous system. The HPA axis integrates physical and psychosocial influences in order to allow an organism to adapt effectively to its environment, use resources, and optimize survival.

Anatomical connections between brain areas such as the amygdala, hippocampus, prefrontal cortex and hypothalamus facilitate activation of the HPA axis. Sensory information arriving at the lateral aspect of the amygdala is processed and conveyed to the amygdala's central nucleus, which then projects out to several parts of the brain involved in responses to fear. At the hypothalamus, fear-signaling impulses activate both the sympathetic nervous system and the modulating systems of the HPA axis.

Increased production of cortisol during stress results in an increased availability of glucose in order to facilitate fighting or fleeing. As well as directly increasing glucose availability, cortisol also suppresses the highly demanding metabolic processes of the immune system, resulting in further availability of glucose.

Glucocorticoids have many important functions, including modulation of stress reactions, but in excess they can be damaging. Atrophy of the hippocampus in humans and animals exposed to severe stress is believed to be caused by prolonged exposure to high concentrations of glucocorticoids. Deficiencies of the hippocampus may reduce the memory resources available to help a body formulate appropriate reactions to stress.

Immune system

There is bi-directional communication and feedback between the HPA axis and the immune system. A number of cytokines, such as IL-1, IL-6, IL-10 and TNF-alpha can activate the HPA axis, although IL-1 is the most potent. The HPA axis in turn modulates the immune response, with high levels of cortisol resulting in a suppression of immune and inflammatory reactions. This helps to protect the organism from a lethal overactivation of the immune system, and minimizes tissue damage from inflammation.

The CNS is in many ways "immune privileged", but it plays an important role in the immune system and is affected by it in turn. The CNS regulates the immune system through neuroendocrine pathways, such as the HPA axis. The HPA axis is responsible for modulating inflammatory responses that occur throughout the body.

During an immune response, proinflammatory cytokines (e.g. IL-1) are released into the peripheral circulation system and can pass through the blood–brain barrier where they can interact with the brain and activate the HPA axis. Interactions between the proinflammatory cytokines and the brain can alter the metabolic activity of neurotransmitters and cause symptoms such as fatigue, depression, and mood changes. Deficiencies in the HPA axis may play a role in allergies and inflammatory/ autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis.

When the HPA axis is activated by stressors, such as an immune response, high levels of glucocorticoids are released into the body and suppress immune response by inhibiting the expression of proinflammatory cytokines (e.g. IL-1, TNF alpha, and IFN gamma) and increasing the levels of anti-inflammatory cytokines (e.g. IL-4, IL-10, and IL-13) in immune cells, such as monocytes and neutrophils

The relationship between chronic stress and its concomitant activation of the HPA axis, and dysfunction of the immune system is unclear; studies have found both immunosuppression and hyperactivation of the immune response.

Stress

Schematic overview of the hypothalamic-pituitary-adrenal (HPA) axis. Stress activates the HPA-axis and thereby enhances the secretion of glucocorticoids from the adrenals.

Stress and disease

The HPA axis is involved in the neurobiology and pathophysiology of mood disorders and functional illnesses, including anxiety disorder, bipolar disorder, insomnia, posttraumatic stress disorder, borderline personality disorder, ADHD, major depressive disorder, burnout, chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and alcoholism. Antidepressants, which are routinely prescribed for many of these illnesses, serve to regulate HPA axis function.

Sex differences are prevalent in humans with respect to psychiatric stress-related disorders such as anxiety and depression, where women experience these disorders more often than men. Particularly in rodents, it has been shown that females may lack the ability to tolerate as well as process stress (particularly for chronic stress) due to possible down regulation of glucocorticoid receptor expression as well as a deficiency of FKBP51 binding protein in the cytosol. By constantly activating the HPA axis, this could lead to higher instances of stress and disorders that would only get worse with chronic stress. Specifically in rodents, females show greater activation of the HPA axis following stress than males. These differences also likely arise due to the opposing actions that certain sex steroids have, such as testosterone and oestrogen. Oestrogen functions to enhance stress-activated ACTH and CORT secretion while testosterone functions to decrease HPA axis activation and works to inhibit both ACTH and CORT responses to stress. However, more studies are required to better understand the underlying basis of these sex differences.

Experimental studies have investigated many different types of stress, and their effects on the HPA axis in many different circumstances. Stressors can be of many different types—in experimental studies in rats, a distinction is often made between "social stress" and "physical stress", but both types activate the HPA axis, though via different pathways. Several monoamine neurotransmitters are important in regulating the HPA axis, especially dopamine, serotonin and norepinephrine (noradrenaline). There is evidence that an increase in oxytocin, resulting for instance from positive social interactions, acts to suppress the HPA axis and thereby counteracts stress, promoting positive health effects such as wound healing.

The HPA axis is a feature of mammals and other vertebrates. For example, biologists studying stress in fish showed that social subordination leads to chronic stress, related to reduced aggressive interactions, to lack of control, and to the constant threat imposed by dominant fish. Serotonin (5HT) appeared to be the active neurotransmitter involved in mediating stress responses, and increases in serotonin are related to increased plasma α-MSH levels, which causes skin darkening (a social signal in salmonoid fish), activation of the HPA axis, and inhibition of aggression. Inclusion of the amino acid L-tryptophan, a precursor of 5HT, in the feed of rainbow trout made the trout less aggressive and less responsive to stress. However, the study mentions that plasma cortisol was not affected by dietary L-tryptophan. The drug LY354740 (also known as Eglumegad, an agonist of the metabotropic glutamate receptors 2 and 3) has been shown to interfere in the HPA axis, with chronic oral administration of this drug leading to markedly reduced baseline cortisol levels in bonnet macaques (Macaca radiata); acute infusion of LY354740 resulted in a marked diminution of yohimbine-induced stress response in those animals.

Studies on people show that the HPA axis is activated in different ways during chronic stress depending on the type of stressor, the person's response to the stressor and other factors. Stressors that are uncontrollable, threaten physical integrity, or involve trauma tend to have a high, flat diurnal profile of cortisol release (with lower-than-normal levels of cortisol in the morning and higher-than-normal levels in the evening) resulting in a high overall level of daily cortisol release. On the other hand, controllable stressors tend to produce higher-than-normal morning cortisol. Stress hormone release tends to decline gradually after a stressor occurs. In post-traumatic stress disorder there appears to be lower-than-normal cortisol release, and it is thought that a blunted hormonal response to stress may predispose a person to develop PTSD.

It is also known that HPA axis hormones are related to certain skin diseases and skin homeostasis. There is evidence shown that the HPA axis hormones can be linked to certain stress related skin diseases and skin tumors. This happens when HPA axis hormones become hyperactive in the brain.

Stress and development

Prenatal stress

There is evidence that prenatal stress can influence HPA regulation. In animal experiments, exposure to prenatal stress has been shown to cause a hyper-reactive HPA stress response. Rats that have been prenatally stressed have elevated basal levels and abnormal circadian rhythm of corticosterone as adults. Additionally, they require a longer time for their stress hormone levels to return to baseline following exposure to both acute and prolonged stressors. Prenatally stressed animals also show abnormally high blood glucose levels and have fewer glucocorticoid receptors in the hippocampus. In humans, prolonged maternal stress during gestation is associated with mild impairment of intellectual activity and language development in their children, and with behaviour disorders such as attention deficits, schizophrenia, anxiety and depression; self-reported maternal stress is associated with a higher irritability, emotional and attentional problems.

There is growing evidence that prenatal stress can affect HPA regulation in humans. Children who were stressed prenatally may show altered cortisol rhythms. For example, several studies have found an association between maternal depression during pregnancy and childhood cortisol levels. Prenatal stress has also been implicated in a tendency toward depression and short attention span in childhood.

Early life stress

The role of early life stress in programming the HPA axis has been well-studied in animal models. Exposure to mild or moderate stressors early in life has been shown to enhance HPA regulation and promote a lifelong resilience to stress. In contrast, early-life exposure to extreme or prolonged stress can induce a hyper-reactive HPA axis and may contribute to lifelong vulnerability to stress. In one widely replicated experiment, rats subjected to the moderate stress of frequent human handling during the first two weeks of life had reduced hormonal and behavioral HPA-mediated stress responses as adults, whereas rats subjected to the extreme stress of prolonged periods of maternal separation showed heightened physiological and behavioral stress responses as adults.

Several mechanisms have been proposed to explain these findings in rat models of early-life stress exposure. There may be a critical period during development during which the level of stress hormones in the bloodstream contribute to the permanent calibration of the HPA axis. One experiment has shown that, even in the absence of any environmental stressors, early-life exposure to moderate levels of corticosterone was associated with stress resilience in adult rats, whereas exposure to high doses was associated with stress vulnerability.

Another possibility is that the effects of early-life stress on HPA functioning are mediated by maternal care. Frequent human handling of the rat pups may cause their mother to exhibit more nurturant behavior, such as licking and grooming. Nurturant maternal care, in turn, may enhance HPA functioning in at least two ways. First, maternal care is crucial in maintaining the normal stress hypo responsive period (SHRP), which in rodents, is the first two weeks of life during which the HPA axis is generally non-reactive to stress. Maintenance of the SHRP period may be critical for HPA development, and the extreme stress of maternal separation, which disrupts the SHRP, may lead to permanent HPA dysregulation. Another way that maternal care might influence HPA regulation is by causing epigenetic changes in the offspring. For example, increased maternal licking and grooming has been shown to alter expression of the glutocorticoid receptor gene implicated in adaptive stress response. At least one human study has identified maternal neural activity patterns in response to video stimuli of mother-infant separation as being associated with decreased glucocorticoid receptor gene methylation in the context of post-traumatic stress disorder stemming from early life stress. Yet clearly, more research is needed to determine if the results seen in cross-generational animal models can be extended to humans.

Though animal models allow for more control of experimental manipulation, the effects of early life stress on HPA axis function in humans has also been studied. One population that is often studied in this type of research is adult survivors of childhood abuse. Adult survivors of childhood abuse have exhibited increased ACTH concentrations in response to a psychosocial stress task compared to unaffected controls and subjects with depression but not childhood abuse. In one study, adult survivors of childhood abuse that are not depressed show increased ACTH response to both exogenous CRF and normal cortisol release. Adult survivors of childhood abuse that are depressed show a blunted ACTH response to exogenous CRH. A blunted ACTH response is common in depression, so the authors of this work posit that this pattern is likely to be due to the participant's depression and not their exposure to early life stress.

Heim and colleagues have proposed that early life stress, such as childhood abuse, can induce a sensitization of the HPA axis, resulting in particular heightened neuronal activity in response to stress-induced CRH release. With repeated exposure to stress, the sensitized HPA axis may continue to hypersecrete CRH from the hypothalamus. Over time, CRH receptors in the anterior pituitary will become down-regulated, producing depression and anxiety symptoms. This research in human subjects is consistent with the animal literature discussed above.

The HPA axis was present in the earliest vertebrate species, and has remained highly conserved by strong positive selection due to its critical adaptive roles. The programming of the HPA axis is strongly influenced by the perinatal and early juvenile environment, or "early-life environment". Maternal stress and differential degrees of caregiving may constitute early life adversity, which has been shown to profoundly influence, if not permanently alter, the offspring's stress and emotional regulating systems. Widely studied in animal models (e.g. licking and grooming/LG in rat pups), the consistency of maternal care has been shown to have a powerful influence on the offspring's neurobiology, physiology, and behavior. Whereas maternal care improves cardiac response, sleep/wake rhythm, and growth hormone secretion in the neonate, it also suppresses HPA axis activity. In this manner, maternal care negatively regulates stress response in the neonate, thereby shaping his/her susceptibility to stress in later life. These programming effects are not deterministic, as the environment in which the individual develops can either match or mismatch with the former's "programmed" and genetically predisposed HPA axis reactivity. Although the primary mediators of the HPA axis are known, the exact mechanism by which its programming can be modulated during early life remains to be elucidated. Furthermore, evolutionary biologists contest the exact adaptive value of such programming, i.e. whether heightened HPA axis reactivity may confer greater evolutionary fitness.

Various hypotheses have been proposed, in attempts to explain why early life adversity can produce outcomes ranging from extreme vulnerability to resilience, in the face of later stress. Glucocorticoids produced by the HPA axis have been proposed to confer either a protective or harmful role, depending on an individual's genetic predispositions, programming effects of early-life environment, and match or mismatch with one's postnatal environment. The predictive adaptation hypothesis (1), the three-hit concept of vulnerability and resilience (2) and the maternal mediation hypothesis (3) attempt to elucidate how early life adversity can differentially predict vulnerability or resilience in the face of significant stress in later life. These hypotheses are not mutually exclusive but rather are highly interrelated and unique to the individual.

(1) The predictive adaptation hypothesis: this hypothesis is in direct contrast with the diathesis stress model, which posits that the accumulation of stressors across a lifespan can enhance the development of psychopathology once a threshold is crossed. Predictive adaptation asserts that early life experience induces epigenetic change; these changes predict or "set the stage" for adaptive responses that will be required in his/her environment. Thus, if a developing child (i.e., fetus to neonate) is exposed to ongoing maternal stress and low levels of maternal care (i.e., early life adversity), this will program his/her HPA axis to be more reactive to stress. This programming will have predicted, and potentially be adaptive in a highly stressful, precarious environment during childhood and later life. The predictability of these epigenetic changes is not definitive, however – depending primarily on the degree to which the individual's genetic and epigenetically modulated phenotype "matches" or "mismatches" with his/her environment (See: Hypothesis (2)).

(2) Three-Hit Concept of vulnerability and resilience: this hypothesis states that within a specific life context, vulnerability may be enhanced with chronic failure to cope with ongoing adversity. It fundamentally seeks to explicate why, under seemingly indistinguishable circumstances, one individual may cope resiliently with stress, whereas another may not only cope poorly, but consequently develop a stress-related mental illness. The three "hits" – chronological and synergistic – are as follows: genetic predisposition (which predispose higher/lower HPA axis reactivity), early-life environment (perinatal – i.e. maternal stress, and postnatal – i.e. maternal care), and later-life environment (which determines match/mismatch, as well as a window for neuroplastic changes in early programming). The concept of match/mismatch is central to this evolutionary hypothesis. In this context, it elucidates why early life programming in the perinatal and postnatal period may have been evolutionarily selected for. Specifically, by instating specific patterns of HPA axis activation, the individual may be more well equipped to cope with adversity in a high-stress environment. Conversely, if an individual is exposed to significant early life adversity, heightened HPA axis reactivity may "mismatch" him/her in an environment characterized by low stress. The latter scenario may represent maladaptation due to early programming, genetic predisposition, and mismatch. This mismatch may then predict negative developmental outcomes such as psychopathologies in later life.

Ultimately, the conservation of the HPA axis has underscored its critical adaptive roles in vertebrates, so, too, various invertebrate species over time. The HPA axis plays a clear role in the production of corticosteroids, which govern many facets of brain development and responses to ongoing environmental stress. With these findings, animal model research has served to identify what these roles are – with regards to animal development and evolutionary adaptation. In more precarious, primitive times, a heightened HPA axis may have served to protect organisms from predators and extreme environmental conditions, such as weather and natural disasters, by encouraging migration (i.e. fleeing), the mobilization of energy, learning (in the face of novel, dangerous stimuli) as well as increased appetite for biochemical energy storage. In contemporary society, the endurance of the HPA axis and early life programming will have important implications for counseling expecting and new mothers, as well as individuals who may have experienced significant early life adversity.