Psychoneuroendocrinology

from Wikipedia, the free encyclopedia

The Psycho Euro endocrinology studies the interrelationships between behavior and experience on the one hand, and endocrine functions on the other. PNE is a relatively young discipline, like scientific psychology as a whole. The aim is to research mental and neurological diseases. However, these research areas are still at the basic research stage.

There are several related scientific disciplines , some of which overlap in their research areas:

Research subject of psychoneuroendocrinology

→ Main article hormones

In psychoneuroendocrinology, endocrine processes are examined in the context of psychology. The subject of research are hormonal processes mainly of the following endocrine glands:

In general, hormones can be defined as chemical signal substances that are produced in special cells and usually transported to different parts of the body via the bloodstream. There they show their specific effect. Basically, this effect is developed through binding to a receptor . A distinction is made between exocrine and endocrine glands. Endocrine glands secrete hormones directly into the blood , lymph, or tissue ; Exocrine glands deliver their secretions to an inner or outer surface of the body via an outlet duct. Neurotransmitters are differentiated from hormones . These messenger substances are released into the synaptic gap between two nerve cells in order to develop their effect on the postsynaptic nerve cell. There are also functional intermediate forms (between hormones and neurotransmitters), so-called neuropeptides . Furthermore, different classes of messenger substances can be distinguished depending on their chemical structure: steroid hormones and other substances, amino acid derivatives , peptide hormones or protein hormones .

Routes of communication by hormones

In order to be able to work according to their function, hormones have to communicate with the body. Four different communication channels are largely occupied.

The synaptic communication in chemical synapses made by the release of a transmitter . This diffuses through the synaptic gap and then acts on another cell. As autocrine secretion communication of hormones is known that affect not only other cells, but also influence by feedback mechanism own cell. Paracrine secretion refers to the release of hormones from a cell that diffuse through the extracellular space and affect the immediately neighboring cells. In endocrine communication, hormones are formed in an endocrine gland and released into the bloodstream and can thus influence all body cells with the corresponding receptor. Neuroendocrine communication is a sub-category of endocrine communication. The endocrine cell is influenced by synaptic communication to release the hormone in the bloodstream.

Homeostasis

Basically, the body strives for homeostasis , i.e. balance, in endocrine communication . Endocrine control and feedback mechanisms restore the balance. Either this is achieved through the irregular hormone release, which often follows a circadian rhythm , or the cell uses the auto- and paracrine feedback processes already described. The latter is particularly important for the reciprocal communication between the brain and the body periphery.

Hormone axes

In the following, the two best-studied hormone axes in psychoendocrinology, the HHNA and the HHGA, are presented in more detail. Both represent a cycle that is regulated by feedforward and feedback processes: The signal transmission begins with an impulse from the hypothalamus , which results in the release of hormones into the blood at the respective target gland. Finally, feedback mechanisms to the hypothalamus prevent further hormone release.

Hypothalamic-Pituitary-Adrenal Axis (HHNA)

→ Main article hypothalamic-pituitary-adrenal axis

The HHNA shows a circadian rhythm, but also plays a central role in the body's stress response and is therefore of central importance for psychoneuroendocrinology. When a stressor occurs, such as the sudden sound of a siren, CRH is released into the blood in the hypothalamus , which binds to receptors in the anterior pituitary gland . This reacts by releasing ACTH , which in turn is transported via the bloodstream to the adrenal cortex and there binds to receptors. Eventually, as a result, the adrenal cortex releases corticoids such as cortisol . These hormones initiate the actual stress response, also known as the fight-or-flight response: the blood sugar level rises, blood pressure is increased, the immune system is largely suppressed and digestive processes are reduced. This feedforward cascade is countered by feedback processes to regulate the stress response: By binding the glucocorticoids to corticosteroid receptors in the hypothalamus and the pituitary gland, the further release of hormones in both brain areas is finally prevented, which in turn prevents an increased release of cortisol in the adrenal glands and restores homeostasis .

Hypothalamic-Pituitary-Gonadal Axis (HHGA)

The HHGA regulates the production and release of sex hormones and is sometimes very different in men and women. While hormone production in women depends on the course of the menstrual cycle , in men it is largely continuous over time. Regardless of gender, the signaling cascade begins with the release of GnRH in the hypothalamus. By binding GnRH to receptors in the anterior pituitary gland, it releases both LH and FSH , which travel to the gonads via the bloodstream . Here the production and release of the respective sex hormones is stimulated. As gender-specific hormones released in the gonads eventually bind to receptors in the hypothalamus and pituitary gland, a negative feedback mechanism takes place. The release of GnRH as well as LH and FSH will be shut down as a result.

Entanglements with psychoneuroimmunology

A neighboring field of psychoneuroendocrinology is psychoneuroimmunology . This research area deals in particular with the interactions of the immune system with the psyche and nervous system. A clear separation between the specialist areas is hardly possible, since the nervous system , endocrine system and immune system are interlinked in many ways. They maintain homeostasis together and in constant exchange . In the following, the interactions between the neuroendocrine system and the immune system are presented in more detail and then explained using examples.

Influences of the (neuro-) endocrine system on the immune system

The neuroendocrine system influences the immune system in three main ways: via nerve endings of the sympathetic nervous system (SNS), via hypothalamic and pituitary hormones and via neuropeptides .

The autonomic nervous system, to which the sympathetic nervous system belongs, supplies all tissues of the immune system, such as the bone marrow, thymus gland, spleen and lymph nodes, with nerve stimuli. The innervation of sympathetic postganglionic neurons connects the central nervous system (CNS) and the immune system. Immune cells express receptors for noradrenaline (the primary neurotransmitter of the SNS), but also for other neurotransmitters such as serotonin , substance P , acetylcholine or histamine . Neurotransmitter activity at these receptors affects immune activity.

In addition to receptors for neurotransmitters, immune cells also express receptors for hormones, so that the hormone level in the bloodstream influences immune activity. Some hormonal influences on the immune system can be found in the examples.

The thymosins form another instance . Thymosins are hormones that are synthesized in the thymus and influence neuronal, endocrine and immunological processes. Within the immune system, thymosins mainly influence the synthesis, differentiation and activation of T cells . Since thymosins are able to cross the blood-brain barrier , they are also active in the central nervous system, where they stimulate the release of neuropeptides and neurotransmitters.

Influences of the immune system on the (neuro-) endocrine system

The immune system communicates with the central nervous system via the vagus nerve , in that the detection of inflammations in the body is passed on to the brain with the help of it.

In addition, cytokines (the messenger substances of the immune system) also have an influence on the neuroendocrine system. They can be transported through the blood-brain barrier and there bind to specific receptors. This allows them to modulate the activity in the hypothalamus and thus influence the release of releasing hormones. In the pituitary gland , too , cytokines can influence the production of glandotropic hormones . Finally, cytokines can also have a direct effect on hormone production in the peripheral hormonal glands such as the thyroid , adrenal glands or gonads . Each cytokine has specific effects and is not necessarily active at all levels. The exact effect of individual cytokines on the neuroendocrine system is only partially known and is being researched further.

Examples

HHNA

Influences of the endocrine system on the immune system

The glucocorticoids released by the HHNA have powerful anti-inflammatory properties. During stress, glucocorticoids are released which exert regulatory control over stress-induced inflammatory reactions. The suppressive effect on the immune system ( immunosuppression ) prevents tissue damage. In addition, the glucocorticoids strengthen the function of T cells and the reactions to antigens (stimulating effect) in certain situations . These anti-inflammatory processes result mainly from genomic effects. Thus, glucocorticoids reduce the expression of proinflammatory cytokines, while they increase the expression of antiinflammatory cytokines .

Influences of the immune system on the endocrine system

All levels of HHNA signaling are regulated by cytokines. In particular, interleukin-6 plays a role, which increases due to immune activation and acute stress and is colocalized in the pituitary gland. There it influences the hormone production and ensures increased glucocorticoid levels. It is also expressed together with CRH and ADH in the hypothalamus, where it increases CRH expression and secretion, which in turn is reflected in increased ACTH levels. In addition, glucocorticoid signal transmission paths are interrupted at various points by proinflammatory cytokines and the function of the glucocorticoids is thus interrupted. It is thus clear that the HHNA is regulated to a large extent by the immune system. These effects are often in the form of negative feedback that prevents over-enhancement or damage from immune activation. This means that as the inflammation increases, the glucocorticoids will rise. This inhibits the immune system, controls the immune response and so z. B. prevents the development of autoimmune diseases .

HHGA

Although both sexes have the same immunological cell types and communication channels, they differ in the way they react immunologically. Women tend to have a higher immune response than men. 80% of all patients with autoimmune diseases (e.g. rheumatism or multiple sclerosis ) are female. One reason for this difference is that gonadal sex hormones, such as B. estradiol , progesterone and testosterone , regulate the immunological cell response to pathogens by z. B. bind to sex hormone receptors of the immune system. Since women and men have different sex hormone profiles, they also have different immune defenses.

Differences in immune defense can also be found in the context of the female menstrual cycle . In the premenstrual phase, autoimmune diseases and asthma exacerbate symptoms, probably due to the strong fluctuations in progesterone and estradiol levels. A similar physiological variation in the immune response could possibly also take place during the implantation of the embryo and throughout pregnancy. Compared to the follicular phase , which is characterized by a high estradiol and a low progesterone level, the circulating T-cell level decreases in the luteal phase , in which the progesterone level is higher. A significant physiological change during pregnancy is a temporary breakdown of the thymus , which returns to its original level after birth. This thymus atrophy is caused by the high levels of estradiol and progesterone. The resulting impaired immune system functions may be necessary to prevent rejection of the fetus and to ensure the continuation of the pregnancy.

Even outside of pregnancy, the sex hormones have a strong effect on the thymus: They promote involution (natural regression of an organ) and thus lead to the aging of the immune system. A neutering can make this effect reversed. It could be shown that the atrophy of the thymus epithelium is eliminated and the number of T cells increases (Sutherland et al. 2005).

Determination of endocrinological parameters

Suitable biological materials

In general, the levels of endocrine secretion (for example the release of the stress-associated hormone cortisol) can be analyzed in a variety of biological materials, such as blood , saliva , urine , liquor , tissue or hair .

Blood is suitable for recording the total hormone concentration (i.e. the free, biologically active and the bound, biologically inactive components) over very short periods of time (a few minutes). One disadvantage is that it is an invasive method and therefore possibly a confounding variable when recording stress hormones.

Saliva is suitable for recording the freely circulating hormone levels over very short periods of time (a few minutes). Sampling is minimal and non-invasive.

Urine is suitable for recording the freely circulating hormone levels over medium periods (a few hours to a maximum of one day). Again, it is a non-invasive method.

Hair is well suited as a long-term measure over weeks to months. Sampling is very easy and non-invasive. Disadvantages are that no data can be obtained with very short hair and the method cannot be used for substances that are metabolized too quickly to be incorporated into growing hair, as well as hydrophilic and oversized substances.

In general, it is assumed that human hair grows about 1 cm per month, but studies have now found a considerable variability in growth rates between individual individuals, but also between sexes and ethnicities as well as depending on the scalp areas considered, which is what the analysis and especially the comparison collected values ​​must be observed.

Analytical methods for determining hormone concentrations

Quantitative immunassays use specific antigen-antibody reactions . An antibody binds to a specific antigen determinant ( epitope ) of the hormone to be determined. A distinction can be made between the competitive and non-competitive approaches. With either method, the unknown amount of antigen (i.e., the amount of hormones) in the sample solution cannot be directly described. Instead, the measurement data obtained through the test procedure must be compared with a standard or determined using a standard curve.Depending on the marker substance used, which is necessary to visualize the amount of hormones, one speaks of enzyme immunoassays (ELISA), radioimmunoassays (RIA), fluorineimmunoassays (FIA) and luminescence immunoassays (LIA).

Chromatographic detection methods: In addition to quantitative immunoassays, chromatographic methods represent a second common group of methods used to determine the concentration of hormones. In endocrinology, gas chromatography or liquid chromatography is oftenused, in which the sample is passed through the chromatograph in its gaseous or liquid state. Different substances contained require different lengths of time to pass through the device. A detector at the end of the chromatograph can therefore generate a signal that provides information about the composition of the sample.

Example: analysis of cortisol

One of the most important and most frequently measured hormones in the context of psychoendocrinology is the steroid hormone cortisol. The cortisol level follows a circadian rhythm with a peak in the morning and a subsequent decrease during the day. In addition, cortisol is central to the physiological stress response. Cortisol can be determined from saliva, urine and blood for questions regarding short-term processes (for example with regard to the reaction to acute stress), but the hair cortisol analysis is best suited for displaying longer periods of time. After a few preprocessing steps (washing to remove sweat, sebum and other possibly adulterating substances; drying; weighing in to calculate the hormone concentration in relation to the mass; crushing; extraction of cortisol using organic solvents in several steps) the analysis by means of immunoassay or chromatography respectively.

Advantages and disadvantages of the method

In the clinical area, the technology is widely used as a biomarker for diagnosis, prognosis and management, but above all for research into diseases such as Cushing's syndrome , severe stress, cardiovascular diseases and mental illnesses. However, due to the novelty of the method, some findings on standardization and comparability are still pending.

Diagnostics: stimulation of the endocrine axes

In order to prove whether the functionality of a hormone axis is unrestricted, it may not make sense to only take basal measurements of the hormones involved in, for example, blood, urine, saliva or hair. From these measurements it is not possible to deduce the level at which there is dysregulation in the case of too high or too low values, nor whether, despite an inconspicuous result, there are dysregulations between different levels, but which balance each other out.

With the help of pharmacological function tests, both the feedback sensitivity and the reactivity of a hormone axis can be determined. Due to their agonistic (stimulating) or antagonistic (inhibiting) effect, the pharmaceuticals used have effects on the stimulation or suppression of the release of hormones at the respective level of the axis.

The classification of the tests, also known as pharmacological provocation tests, can be carried out on the basis of the axis influenced and the level of regulation.

1. A central effect is triggered by pharmacologically triggering a physiological stressor

2. Pharmaceuticals that pass through the blood-brain barrier influence the release of releasing hormones by acting as receptor ligands for the respective neurotransmitters

3. The release of the Endohormons a particular axis of hormone glands will be by the administration of synthetic Tropinen obtained

4. To check the functionality of the feedback loop, the respective endohormone is greatly increased by administration, or the concentration is reduced by hindering the synthesis.

In addition to pharmacological function tests, research also uses stimulation of the HHNA using artificially generated stressors. The Trier Social Stress Test (TSST) can be used for this. The TSST is the most widely used standardized psychological stress test , which has been proven to lead to an increase in HHNA activity.

Summary of some important endocrinological tests

The insulin tolerance test (ITT) triggers hypoglycemia through various intermediate steps. This acts as a stressor. It is used for diagnosing the hypothalamic-pituitary-adrenal axis (HHNA), the hypothalamic-pituitary-somatotropic system and the hypothalamic-pituitary prolactinergic system.

Naloxone is an opiate antagonist that blocks the release of CRH and GnRH . The naloxon test thus leads to an increase in the HHNA and hypothalamus-gonadal axis activity.

CRH , TRH and GnRH stimulation tests have a pituitary effect and trigger an increase in the respective tropines ( ACTH , TSH or LH and FSH ). Dysregulation at the pituitary level is examined.

Dexamethasone particularly binds to the glucocorticoid receptors of the pituitary gland . This leads to a suppression of the ACTH and consequently the cortisol release. The dexamethasone suppression test can also be performed in conjunction with an HHNA stimulation test if abnormal cortisol suppression is suspected. Hyperactive CRH neurons in the hypothalamus are considered to be the cause of a possible reduced effect of the DEX test.

Other checking options are the fenfluramine , L-Dopa , metroclopramide , ACTH , glucose suppressions and clonidine tests.

Potential confounding variables

In psychoneuroendocrine studies, certain factors can affect the results and should therefore be taken into account in the studies. At the same time, they could provide an explanation for the heterogeneity of the existing findings. These factors include, for example, the gender, age and body mass index (BMI) of people.

While there are large gender differences with regard to a large number of psychological processes and clinical diseases, there are also endocrine differences. For example, studies suggest that men have higher basal cortisol levels compared to women. Different gender ratios in studies could therefore contribute to the heterogeneity of the findings.

In many studies, altered endocrine processes with age showed, for example, an increasing daily cortisol secretion, possibly by a reduced number of mineralocorticoid receptor (MRs) and glucocorticoid receptors (GRs), leading to increased CRH - secretion and as a consequence to increased ACTH - and cortisol release.

There is much evidence that a high BMI and an increased waist-to-hip ratio can be associated with altered psychoendocrine processes, such as: B. is associated with an increased basal cortisol level. The reason for this has not been finally clarified.

Clinical research fields in psychoneuroendocrinology

stress

Possible endocrine processes in the context of stress

An important research area of ​​PNE deals with the connection between stress and the potentially subsequent reactions of the neuroendocrinological system. The main focus of research in recent decades has been on recording changes in the functions of the HNNA after the occurrence of stressful life events. One of the most frequently used measures of the functionality of the HNNA in PNE research is the cortisol level. For a long time, PNE research showed great inconsistencies with regard to the direction of the relationship between various stressors and the physiological measures of the stress response of the HNNA function, so that moderator variables of this relationship were researched. Both the characteristics of the stressors and the specific characteristics of the affected persons were discussed.

Possible determinants of psychoendocrine processes in the context of stress

Elapsed time since the stressor appeared

It can be concluded from meta-analytical findings that acute stress is associated with an initial activation of the HNNA. This is expressed, for example, in an increased cortisol wake-up reaction , increased secretion throughout the day, increased ACTH level in the blood and an increased cortisol reaction in the dexamethasone suppression test . With an increasing time interval after the occurrence of the stressor , however, there is a decrease in HNNA activity and thus in the cortisol level, which may drop to hyponormal values, i.e. below the initial level.

Effects of stressor type on the HHNA response

Research suggests that different types of stressors cause different responses in the HNNA. Stressors that threaten the physical integrity of a person and trauma seem to be associated with increased, but flatter, cortisol levels throughout the day. While the secretion in the morning is slightly reduced compared to people who were not exposed to the stressor, the secretion in the afternoon and in the evening is significantly increased. When confronted with social stressors, however, there were indications of increased cortisol levels throughout the day. Both morning cortisol levels and afternoon and evening levels were significantly higher than in people who were not exposed to these stressors. This overall increased HNNA activity is interpreted as functional in the literature, because cortisol provides energy for adaptive behaviors in order to be able to react to potentially emerging stressors (see also: stress reaction ).

Emotions

Emotions can affect both the direction and the extent of the HNNA response in different situations. Thus they represent the psychological link between stressors and the biological processes of the HNNA and are considered to be the strongest determinants for changes in the HNNA functions. Shame is considered a critical emotion related to stress. Stressful situations that evoke shame are mainly associated with higher cortisol levels in the afternoon / evening. Under laboratory conditions, feelings of shame also increase HNNA activation in acute stressful situations. However, this relationship does not seem to apply to prolonged stress , such as veterans suffering from PTSD . Here, shame seems to have an inverse influence on cortisol secretion, as it is associated with decreased cortisol levels.

Furthermore, loss is seen as a potential moderator of the HNNA reaction. It is believed that stress caused by severe loss activates the HNNA. The resulting sustained release of cortisol seems to be linked to the onset of depression . Stress associated with loss is more likely to be associated with a flattened cortisol profile throughout the day, according to research. The morning cortisol level is lower, while the afternoon / evening cortisol level is higher. The release of cortisol is regulated, among other things, through social interactions. Since loss leads to isolation and withdrawal from social activities, this flat cortisol profile could be seen as a result of loss-related depression.

Controllability

Studies on animals and humans in acute stressful situations have already shown that the secretion of cortisol is increased when one has the feeling that one cannot influence the stressor . In the case of chronic stress , however, it is assumed that the perceived uncontrollability of the stressor leads to reduced HNNA activity and thus explains withdrawal and avoidance behavior . In contrast, the perception of control here could activate the HNNA in order to metabolically support active coping strategies .

Studies have shown that the uncontrollability of chronic stress seems to result in a flattened daily rhythm of cortisol release (low values ​​in the morning and less significant decrease in the course of the day) with an overall higher cortisol volume in the body during the day. On the other hand, higher cortisol values ​​were found in the morning when chronic stress was assessed as controllable. Accordingly, the morning activation could help implement appropriate coping strategies .

Post-traumatic stress disorder

The posttraumatic stress disorder (PTSD) is a serious mental illness, the cause of a trauma is due. Trauma as situations of extreme stress can have far-reaching consequences, which can become chronic in the form of PTSD if the outcome is unfavorable. There is evidence from research that symptoms of PTSD can, among other things, be seen as manifestations of stress-induced changes in neurobiological systems. These include neuroendocrinological systems such as the hypothalamic-pituitary-adrenal axis (HHNA), the hypothalamic-pituitary-thyroid axis (HHSA) and various neurotransmitter (e.g. noradrenaline ) and neuropeptide systems (e.g. corticotropin -releasing hormones (CRH)). These systems are parts of neural circuits that are involved in the regulation of stress and anxiety. Changes in these systems as a result of drastic life events such as trauma can be accompanied by an increased sensitivity to stress and have an impact on the synaptic plasticity of brain regions that are involved in fear conditioning processes and the deletion of fearful memory content, which can ultimately contribute to symptoms typical of PTSD.

Hypothalamic-pituitary-adrenal axis

The hypothalamus-pituitary-adrenal cortex axis (HHNA) plays an important role in theories about the development and maintenance of PTSD. Research shows that glucocorticoids contribute to fear conditioning and the erasure of memory content by helping to inhibit the recall of old memory content and to consolidate new memory content.

In the case of those affected, there has so far been a tendency towards increased feedback sensitivity compared to unaffected study groups, i.e. too sensitive feedback to the hypothalamus that there is enough cortisol in the circulation, and consequently a reduced cortisol concentration. In connection with this, a higher binding potential of the glucocorticoid receptors, an increased signal transmission in the peripheral blood cells and an increased CRH level (see below) in the central nervous system are discussed. Initial study results suggest that treatment with hydrocortisone counteracts this and, if administered immediately after the trauma, could prevent the development of PTSD. However, this must be investigated further in future studies.

Corticotropin-releasing hormones and norepinephrine

Another central nervous circuit that could be relevant for the development of PTSD and that is directly related to the above-mentioned findings is the connection of the amygdala and hypothalamus with the locus coeruleus , from which mainly noradrenergic neurons send signals to other regions. The interaction of CRH and noradrenaline in this cycle is discussed in association with increased fear conditioning and the easier storage of emotional memories as well as increased arousal . From the increased CRH level observed in studies in those affected with PTSD, it could therefore be concluded that this cycle is hyperactive and thus that it is easier to learn to fear.

The release of norepinephrine from sympathetic nerve endings also influences the autonomic stress response through the sympathoadrenomedullary system, also known as the fight-or-flight response . During this reaction, the release of adrenaline and noradrenaline from the adrenal medulla is stimulated. It is currently assumed that the reduced concentration of glucocorticoids in those affected with PTSD inhibits this stress response less and thus sustains it longer, which is related to the increased concentration of adrenaline and noradrenaline in the urine, but also symptoms such as hyperarousal or an increased psychophysiological reactivity Might explain memories of the trauma.

Studies show that the administration of adrenergic blockers such as propanolol could have a reducing effect on the physiological reactions to the trauma or the traumatic memories. However, a direct influence on the development of PTSD has not yet been determined and needs to be researched further.

Hypothalamic-pituitary-thyroid axis

Many studies describe a change in the hypothalamic-pituitary-thyroid axis (HHSA) associated with experiencing psychological trauma. The changes affect the concentration of the control hormone thyrotropin (TSH) released by the pituitary gland , as well as the thyroxine produced by the thyroid gland (T4) and the metabolically more active triiodothyronine (T3) that is converted from it .

An increased T3 value can be determined in those affected by PTSD, as well as an increased conversion of T4 to T3. The effect of T3 on PTSD symptoms remains unclear; A connection between increased T3 levels and increased anxiety was suggested. A longitudinal study showed a connection between the severity of hypothyroidism and the severity of the PTSD symptoms. Furthermore, the “attitude” of the HHSA seems to be relatively stable and difficult to change through psychotherapeutic treatment of PTSD.

Interfaces to non-neuroendocrine systems

BDNF (brain-derived neurotrophic factor) is a growth factor that is important for the normal functioning of certain areas in the hippocampus and the amygdala . Chronic stress, such as occurs in PTSD, appears to damage neurons in hippocampal areas and reduce BDNF signal transmission, which could lead to generalized fear reactions. Increased signal transmission in areas of the amygdala, on the other hand, appears to lead to increased consolidation of fear-related memories. The measurement of the BDNF blood concentration in people with PTSD has produced mixed results, but there seems to be an increase in trauma experienced recently and a decrease in trauma that occurred earlier.

Endocannabinoids are neurotransmitters that are involved in erasing fear-related memories. Compensation for the reduced concentration of endocannabinoids, as typically shown by people with PTSD, is being discussed as a therapeutic starting point, but the evidence is currently still too small to be able to make clear statements about the effectiveness of such therapeutic measures.

Depression and burnout

Dysfunctional stress systems are associated with mental disorders such as depression and burnout syndrome . One of the most important stress systems is the hypothalamic-pituitary-adrenal axis (HHNA) , which regulates the release of cortisol . Since both depression and burnout syndrome are strongly associated with stress and have significant symptom overlap, there is ongoing debate as to whether burnout syndrome is a special subgroup of depression or whether they represent two different disorders. A systematic analysis of similarities and differences in the basal HPA axis activity and their response to stress in these two conditions could provide a biological basis and help to clarify this question.

Using various methods, the similarities and differences in basal HHNA activity and their response to stress in people with depression and in people with burnout syndrome can be indicated. In people with depression, many studies show an increased basal level of cortisol in the cortisol wake-up response (CAR) . Interestingly, some studies also suggest that the elevated CAR is mainly found in people with melancholic depression and not also in individuals with atypical depression. These findings support the assumption that there are subtype-specific differences in CAR in depression. In addition, some studies also find an increased cortisol level in the basal salivary glucocorticoid level as well as in the urine and hair cortisol level. No clear statements can yet be made for the cortisol level in blood serum over the course of the day. The TSST also does not provide a clear picture of the cortisol response in current depression; most studies do not find any difference between the groups. In remission , people with previous depression show a generally reduced cortisol secretion in response to the Trier Social Stress Test (TSST). These findings are more consistent, especially in women. Pharmacological function tests provide strong evidence that people with depression have reduced suppression after pharmacological exposure to dexamethasone.

For burnout syndrome, no clear statement can be made with regard to the basal cortisol secretion. The few existing studies show a tendency towards a reduced level of cortisol in the urine, but an increased level in the hair. Across the board, there are more studies that come across reduced levels of cortisol secretion in people with burnout syndrome compared to healthy controls. Regarding the cortisol reactivity in TSST, no clear statements can be made in burnout syndrome, and the situation is also unclear with pharmacological function tests, in which different results can be found.

Overall, it can be said that the greatest limitation in research on burnout syndrome is the inconsistent diagnostic criteria. These lead to poor comparability of the various studies and make it difficult to clarify whether depression and burnout syndrome are the same disorder or not. In addition, the small number of studies on the basal and reactive cortisol release in burnout syndrome also limits the research.

As soon as research has gathered enough knowledge about the role cortisol and other hormones play in the pathogenesis of depression and burnout syndrome, as well as what influence they have on the effectiveness of therapies, these findings could be used for biologically informed diagnosis and therapy . So far, however, the findings have been too heterogeneous.

literature

  • C. Heim, G. Meinlschmidt: Biological foundations. In: U. Ehlert (Ed.): Behavioral medicine. Springer, Berlin 2003, ISBN 3-540-42929-8 , pp. 17-94.
  • Heim, C., & Nemeroff, CB (2016). Neurobiological Pathways Involved in Fear, Stress and PTSD. In Liberzon, I. & Ressler, K. (Eds.), Neurobiology of PTSD: From Brain to Mind (pp. 220-238). England, UK: Oxford University Press.
  • Ulrike Ehlert, Roland von Känel (ed.): Psychoendocrinology and psychoimmunology. Springer, Berlin et al. 2011, ISBN 978-3-642-16963-2 .

Web links

Individual evidence

  1. ↑ a b c d e f g h i j k l m n Ulrike Ehlert, Roland Von Känel: Psychoendocrinology and Psychoimmunology: with 21 tables . Springer, Berlin 2011, ISBN 978-3-642-16963-2 .
  2. ↑ a b c d Michael Wilkinson, Richard E. Brown: An introduction to neuroendocrinology . Cambridge University Press, 2015, ISBN 978-1-139-04580-3 , pp. 351-387 .
  3. ↑ Jayne S. Sutherland, Gabrielle L. Goldberg, Maree V. Hammett, Adam P. Uldrich, Stuart P. Berzins: Activation of Thymic Regeneration in Mice and Humans following Androgen Blockade . In: The Journal of Immunology . tape 175 , no. 4 , August 15, 2005, ISSN  0022-1767 , p. 2741-2753 , doi : 10.4049 / jimmunol.175.4.2741 , PMID 16081852 ( jimmunol.org [accessed May 26, 2020]).
  4. ↑ a b c d Michael JE Greff, Jeffrey M. Levine, Awatif M. Abuzgaia, Abdelbaset A. Elzagallaai, Michael J. Rieder: Hair cortisol analysis: An update on methodological considerations and clinical applications . In: Clinical Biochemistry . tape 63 , January 1, 2019, ISSN  0009-9120 , p. 1–9 , doi : 10.1016 / j.clinbiochem.2018.09.010 ( sciencedirect.com [accessed May 28, 2020]).
  5. ↑ Clemens Kirschbaum, Karl-Martin Pirke, Dirk H. Hellhammer: The 'Trier Social Stress Test' - A Tool for Investigating Psychobiological Stress Responses in a Laboratory Setting . In: Neuropsychobiology . tape 28 , no. 1-2 , 1993, ISSN  0302-282X , pp. 76–81 , doi : 10.1159 / 000119004 ( karger.com [accessed May 28, 2020]).
  6. ↑ a b c d N. Rothe, J. Steffen, M. Penz, C. Kirschbaum, A. Walther: Examination of peripheral basal and reactive cortisol levels in major depressive disorder and the burnout syndrome: A systematic review . In: Neuroscience & Biobehavioral Reviews . February 20, 2020, ISSN  0149-7634 , doi : 10.1016 / j.neubiorev.2020.02.024 ( sciencedirect.com [accessed May 28, 2020]).
  7. ↑ a b c d e f g h Gregory E. Miller, Edith Chen, Eric S. Zhou: If It Goes Up, Must It Come Down? Chronic Stress and the Hypothalamic-Pituitary-Adrenocortical Axis in Humans . In: Psychological Bulletin . tape 133 , no. 1 , 2007, p. 25-45 , doi : 10.1037 / 0033-2909.133.1.25 .
  8. ↑ RM Sapolsky, LM Romero, AU Munck: How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions . In: Endocrine Reviews . tape 21 , 2000, pp. 55-89 .
  9. ↑ a b S. S. Dickerson & ME Kemeny: Acute stressors and cortisol responses: A theoretical integration and synthesis of laboratory research. In: Psychological Bulletin . tape 130 , 2004, pp. 355-391 .
  10. ↑ TL Gruenewald, ME Kemeny, N. Aziz, JL Fahey: Acute threat to the social self: Shame, social self-esteem, and cortisol activity . In: Psychosomatic Medicine . tape 66 , 2004, p. 915-924 .
  11. ↑ Mason, JW, Wang, S., Yehuda, R., Riney, S., Charney, DS, & Southwick, SM: Psychogenic lowering of urinary cortisol levels linked to increased emotional numbing and a shame-depressive syndrome in combat-related posttraumatic stress disorder . In: Psychosomatic Medicine . tape 63 , 2001, p. 387-401 .
  12. ↑ Stetler, C., Dickerson, SS, & Miller, GE: Uncoupling of social zeitgebers and diurnal cortisol secretion in clinical depression . In: Psychoneuroendocrinology . tape 29 , 2004, pp. 1250-1259 .
  13. ↑ Stetler, CA, & Miller, GE: Blunted cortisol response to awakening in mild to moderate depression: Regulatory influences of sleep patterns and social contacts . In: Journal of Abnormal Psychology . tape 114 , 2005, pp. 679-705 .
  14. ^ Gold, PW, & Chrousos, GP: Organization of the stress system and its dysregulation in melancholic and atypical depression: High vs low CRH / NE states . In: Molecular Psychiatry . tape 7 , 2002, p. 254-275 .
  15. ^ Gunnar, MR, & Vazquez, DM: Low cortisol and a flattening of expected daytime rhythm: Potential indices of risk in human development . In: Development and Psychopathology . tape 13 , 2001, p. 515-538 .
  16. ↑ Koob, GF: Corticotropin-releasing factor, norepinephrine, and stress . Ed .: Biological Psychiatry. tape 46 , no. 9 , 1999, p. 1167-1180 .
  17. ↑ a b de Vries, GJ: Posttraumatic stress disorder Prevalence, stress hormones and metabolism . 2019.
  18. ↑ Jung, SJ, Kang, JH, Roberts, AL, Nishimi, K., Chen, Q., Sumner, JA, ... & Koenen, KC: Posttraumatic stress disorder and incidence of thyroid dysfunction in women. Ed .: Psychological medicine. tape 49 , no. 15 , p. 2551-2560 .
  19. ↑ a b c d e N. Rothe, J. Steffen, M. Penz, C. Kirschbaum, A. Walther: Examination of peripheral basal and reactive cortisol levels in major depressive disorder and the burnout syndrome: A systematic review . In: Neuroscience & Biobehavioral Reviews . tape 114 , 2020, ISSN  0149-7634 , p. 232–270 , doi : 10.1016 / j.neubiorev.2020.02.024 ( sciencedirect.com [accessed June 8, 2020]).