Thus, the first phase of the stress response sympathetic adrenomedullar system—SAM , provides a rapid physiological adaptation, resulting in short-lasting responses, such as alertness, vigilance and appraisal of the situation, enabling a strategic decision to face the challenge in the initial phase of a stressful event de Kloet et al.

Whereas, the secondary phase involves the hormonal mechanism Hypothalamic Pituitary adrenal axis—HPA considered sluggish compared to the synaptic mechanisms that activate the SAM, but resulting in an amplified and protracted secretory response long-lasting responses.

Both SAM and HPA axes will be further detailed in the below sections. Thus, when a real stressor is recognized or perceived through signals such as pain, inflammation and others by the brainstem, the neurocircuitry that includes preganglionic autonomic neurons and hypophysiotrophic neurons in the paraventricular nucleus of the hypothalamus PVN are activated, generating a rapid autonomic nervous system ANS and the HPA axis responses as illustrated in Figure 1 ; Ulrich-Lai and Herman, In addition to several nuclei of the brainstem, medullary and spinal cord systems that participate in the activation of ANS through its sympathetic and parasympathetic arms , physical stressors induce the activation of other brain structures that regulates autonomic stress response including PVN, nucleus of the solitary tract NTS and dorsomedial hypothalamus DMH; Geerling et al.

Such structures also have projections to both sympathetic and parasympathetic ANS arms. The PVN contains distinct populations of neurons that project to autonomic targets in the brainstem and spinal cord such as the middle cell column, the parabrachial nucleus, the DMX and NTS and to median eminence sympathetic outflow therefore can be mediated by the PVN, but not exclusively.

Complementary to the PVN role, another important hypothalamic nucleus is the DMH, which houses anatomically segregated neuronal populations responsible for regulating autonomic responses and also important for activating or inhibiting HPA axis activity Ulrich-Lai and Herman, The Locus coeruleus LC; Cunningham and Sawchenko, and rostral ventrolateral medulla RVLM; Dempsey et al.

It is well known that in the brainstem the NTS has an important role in the stress pathways. It is located in a quite strategic position and constitutes a relay for sensory, visceral and somatic information Sapolsky et al.

Moreover, the NTS is directly involved in the control of the cardiovascular and respiratory functions, containing different neuronal groups that receive distinct ascending pathways, as part of the baroreflex and chemoreceptors regulation Machado, ; Zoccal et al.

The NTS also modulates the HPA axis activity mainly through noradrenergic and adrenergic projections to the PVN, but some studies indicate involvement of other catecholaminergic pathways in this modulation Herman et al. Other important structures for triggering the stress response are the circumventricular organs i.

For instance, the activation of the medial parvocellular PVN by the SFO is essential for the central blood pressure regulation by angiotensin II and regulation of drinking behavior Simpson and Routtenberg, ; Hindmarch and Ferguson, And finally, it has also been described that limbic forebrain regions may contribute to physical stressors processing as well, influencing the functions in the autonomic responses to stress and the activation of the HPA-axis Ulrich-Lai and Herman, These limbic stress circuits involve the amygdala, hippocampus and prefrontal cortex PFC that receive associational information from subcortical and cortical areas and their output converge to subcortical relay sites, making downstream processing of limbic information top-down regulation; Ulrich-Lai and Herman, Those circuitries will be explored in the circuits overlapping section and we have highlighted how stressors might interact with the reward approaching × aversion system.

While stressors that are predominantly physically demanding are more likely to evoke autonomic stress responses, psychological uncontrollable and social-evaluative threatening stressors elicit both physical and cognitive stress responses Skoluda et al.

Together with the prosencephalic nuclei, components of limbic circuits such as the PFC, amygdala, hippocampus HIPPO , PVN, ventral tegmental area VTA and nucleus accumbens NAc have a fundamental role in the regulation of stress response Ulrich-Lai and Herman, ; Russo and Nestler, The PFC is critical to develop appropriate responses to environment changes, enabling behavioral plasticity Ridderinkhof et al.

However, the involvement of PFC in stress response is complex, since different anatomic subdivisions play different roles. Bilateral lesions of prelimbic PL cortex portion increases plasma level of adenocorticotrophic hormone ACTH , corticosterone and PVN c-Fos expression Dioro et al.

However, lesions of infralimbic IL cortex reduce corticosterone secretion Sullivan and Gratton, Moreover, studies with animal behaviors showed that lesions in dorsal sites of PFC result in anxiogenic effects, while lesions in ventral sites of PFC have anxiolytic effects Sullivan and Gratton, These data indicate that PL and IL have opposite effects in psychological stressors response, inhibiting PVN activity with anxiolytic effects or stimulating PVN with anxiogenic behaviors, respectively Radley et al.

Despite the functional connection between PFC and PVN, anatomical studies indicate that PFC only has indirect projections to PVN Herman et al.

The PL innervates several GABAergic neurons in the BST, which induces inhibition of PVN, whereas it is suggested that IL pathway projects to non-GABAergic in the BST to stimulate the PVN Radley, However, it remains to be elucidated the exact pathways between PVN and PFC Bains et al.

The PFC also has major projections to the amygdala, an important structure associated with emotional processing Gabbott et al. Initially, the entire amygdala complex appears to promote synthesis and secretion of corticosteroids Kawakami et al. However, subsequent studies showed that amygdala subnuclei have distinct roles in stress response Roozendaal et al.

The amygdala complex can be divided in the basolateral nucleus BLA , the central nucleus of the amygdala CeA and the medial nucleus MeA.

Among these, the BLA has a major role in processing psychological stressors Janak and Tye, , being mainly activated by anticipatory stressors Cullinan et al. However, BLA does not affect corticosterone release itself Seggie, The role of BLA in the processing of psychological stressors seems to be more critical to the consolidation of aversive memories Roozendaal et al.

Intra-BLA infusions of GABAergic receptor agonists impair aversive memory consolidation Brioni et al. Besides, after emotional arousal, BLA neurons show lasting increases in the spontaneous firing rates, which could facilitate the consolidation of emotional memories through synaptic plasticity changes Pelletier et al.

Alterations in emotional and associative learning i. In specific, some studies indicate that BLA-PFC pathway plays a major role in memory consolidation and stress response Laviolette and Grace, ; Felix-Ortiz et al. The BLA have extensive bi-directional monosynaptic glutamatergic projections with PFC PL and IL; Gabbott et al.

Finally, the activity of stress response in the BLA is probably not only dependent on interactions with PFC, but also mediated by projections between PVN and amygdala Prewitt and Herman, The BLA has abundant output to the CeA and MeA, which have multisynaptic connections to the PVN Herman et al.

The CeA and MeA innervate brainstem structures that directly projects to PVN, such as the bed nucleus of the stria terminalis BNST; Prewitt and Herman, However, recent evidence with optogenetics approaches indicates that PVN projections to the CeA are activated during retrieval of long-term fear memories.

In contrast, retrieval of short-term memories is mostly dependent on PFC inputs to the BLA, indicating a time-dependent shift in fear memories circuits Do-Monte et al. In turn, CeA has direct connections to periaqueductal gray PAG , a fundamental area that organizes the threat response LeDoux, Specifically, dorsal PAG is related to unconditioned threats exposure and ventral PAG is activated in conditioned threats, each one with distinct behavioral outputs.

While lesions in dorsal PAG increased freezing behavior, damage to the ventral PAG decreased freezing De Oca et al. Another important limbic structure for stress processing is the hippocampal formation McEwen et al.

While the DG receives most of extra-hippocampal afferents from the entorhinal cortex via the perforant path Witter, , the CA1 and subiculum pyramidal neurons are the main HIPPO output to several areas, such as excitatory projections to PFC PL and IL and indirect inhibitory projections to PVN Barbas and Blatt, ; Herman and Mueller, The hippocampal inhibitory control over the HPA axis acts in a negative feedback manner inhibiting it Jacobson and Sapolsky, ; Herman et al.

The mainly indirect hypothalamic input of HIPPO originates in the CA1 and subiculum that densely innervate BNST and hypothalamic structures, except PVN Canteras and Swanson, ; Cullinan et al. Projections from HIPPO to both the PFC and BLA present some of the most important role in memory but especially for the regulation of psychological stress response Godsil et al.

HIPPO has bidirectional connections with BLA, but at the same time allows PFC to modulate the stress system with a top-down control Mcdonald, ; Janak and Tye, ; Radley et al. However, the CA1 and subiculum monosynaptic glutamatergic efferents to PL and IL can become functionally disrupted after intense psychological stress Zheng and Zhang, In a strong emotional experience, HIPPO and BLA rapidly activate memory-related mechanisms of synaptic plasticity while PFC functioning is suppressed, promoting long-lasting flashbulb memories Diamond et al.

Therefore, in the presence of psychological stressors, if the activity of the amygdala and HIPPO becomes more prevalent, the stress system can switch to a bottom-up control Arnsten, On top of that, prolonged psychological stress decreases glutamatergic projection to interneurons in BLA, leading to loss of BLA inhibition by the PFC and finally, to the hyperexcitability of BLA, which is responsible for behavioral abnormalities related to stress Wei et al.

At this point, among several hypothalamic nuclei that are directly involved in regulating HPA axis and autonomic responses to stressors, the PVN stands out as the principal integrator of stress signals Herman et al.

In general, the medial parvocellular neurons of the PVN receive projections of first or second order of somatic afferent nociceptive, visceral, humoral or sensory pathways, beyond those of the limbic and reward system such as PFC, amygdala, HIPPO, VTA and NAc Russo and Nestler, ; Bains et al.

As already mentioned before, most limbic—PVN connections are indirect and are made through GABAergic cell groups in the BNST and peri-PVN regions of the hypothalamus Crestani et al. Studies involving activity mapping mostly c-Fos expression have demonstrated an important role for BNST in the regulation of the HPA axis Zhu et al.

In the reward system, pharmacological inhibition of NAc increased c-Fos expression in PVN Noh et al. Lastly, the parvocellular neurons of the PVN are strategically connected with several brainstem and forebrain nuclei such as NTS, DMH, LC, VLM, DMX and NA, important to the processing and integration of both modalities of stressors, physical and psychological, which results in a rapid activation of the HPA axis Ulrich-Lai and Herman, ; Senst and Bains, Many of the above circuitry and brain areas responsible for physical and psychological stressors may sound exclusively related to brainstem and forebrain, respectively.

However, some structures are also engaged with different modalities of stressor Figure 2. The best-characterized reward circuit in the brain is made up of dopaminergic neurons in the VTA that project to the NAc, a subdivision of the ventral striatum Bath et al.

The primary brain reward centers are inter-connected in complex ways in the brain reward circuitry, but mostly VTA and NAc regulates limbic areas mentioned above Heshmati and Russo, The dopaminergic tonus of VTA is fundamental to the recognition of rewards or punishment in the environment Russo and Nestler, On the other hand, the optogenetic stimulation of VTA dopaminergic neurons drives to a conditioned place preference Tsai et al.

However, VTA is composed by different neuronal subpopulations, which participate in distinct circuits that encode different motivational signature Lammel et al. Dopaminergic neurons of VTA project to NAc, HIPPO, BLA and PFC, however, the NAc also receives glutamatergic innervations from ventral HIPPO, BLA and PFC Russo and Nestler, ; Lammel et al.

Indeed, dopaminergic neurons that innervate the mPFC show reduced firing after social defeat chronic stress Chaudhury et al. Dopaminergic neurons in VTA exhibit two patterns of spontaneous firing activity: a slow-frequency, single-spike firing and a burst firing, effectively regulating the activity of neurons in dopaminergic target areas and encoding reward-related signals Grace et al.

This mechanism of encoding and engaging specific networks makes sense since the behavioral response to a rewarding approach vs. an aversive experience aversion is different and therefore involves different, perhaps overlapping, neural circuits Lammel et al.

Accordingly, associating this fined-tuned VTA regulation to the stress processing, it has been proposed that a specific ventral VTA pathway is related to painful physical stress. Several findings showed that dopaminergic cells that specifically project to the mPFC regulate the process of noxious stimuli Abercrombie et al.

But it is important to mention that although dopamine has a central role in processing physical stressors, in this scenario, the NAc detains the central role in regulating the reward system Grace et al. Essentially, HIPPO projections to NAc promote susceptibility to psychological stress, BLA-NAc pathway increases reward seeking behavior and PFC-NAc promotes resilience Stuber et al.

Increased firing of VTA dopaminergic neurons that innervate the NAc occurs only in susceptible mice after chronic social defeat stress, while VTA-PFC pathway reduced firing after the same protocol Chaudhury et al. Therefore, we can see that while mesocortical pathways encode physical processing, the NAc may represent an important hub in processing psychological stress.

Not only the PFC activity corresponds to an integrative hot point of limbic and reward circuitry, but also its contribution to the inhibition of the HPA axis by PFC top-down control is crucial. If the inhibitory HPA axis feedback does not function properly, as in the case of chronic stress and neuropsychiatric disorders, the loss of negative feedback in the PVN regulated by the PFC and HIPPO, associated to the hyperexcitability of BLA and silencing of NAc creates a positive feedback in the PVN that can both overload the stress system Duvarci and Paré, ; Willner et al.

Also, regarding the PFC, interesting data have revealed that stimulation of PL enhances hypoxia-mediated corticosterone responses and PVN by using c-Fos activation mapping Jones et al.

Some brainstem nuclei that regulate autonomic response, such as DMX and NAc, receive and send information from and to other regions of the CNS, respectively, including IL and PL portions of PFC, the CeA and BNST Ulrich-Lai and Herman, The CeA, previously mentioned as a central hub in fear response is also considered as a key node for stress integration Ulrich-Lai and Herman, Moreover, NTS is also densely innervated by afferent projections from the CeA Smith and Vale, The NTS can be activated during conditioning paradigms, suggesting that this pathway also plays a role in the integration of anticipatory stress Pezzone et al.

It is important to highlight that different modalities of stressors that activate the PVN also activate the LC-Norepinephrine LC-NE system, such as restraint, shock notably unpredictable , audiogenic stress, autonomic and immunological challenges and also social stress Wood and Valentino, The LC is a compact pontine nucleus adjacent to the fourth ventricle and houses the majority of the NE-expressing neurons in the brain and innervates the entire neuraxis Swanson and Hartman, Activation of the LC-NE occurs in parallel and coordinated with PVN activation.

This cross-talk between those nuclei allows a cognitive processing of the stress response engaging limbic and prosencephalic regions, such as the HIPPO and cortex, which govern neuronal excitability, cognition, memory and complex behaviors Joëls and de Kloet, ; Wood and Valentino, Recent techniques, such as chemogenetics, optogenetics, combined with traditional retrograde tracing, which enable selective manipulation of LC-NE system in rodents, determined the pivotal role of the LC-NE, for example, for stress-induced anxiety-like behavior McCall et al.

Interestingly, Corticotrophin Release Hormone CRH , which initially was discovered and defined as the hormone that initiates the cascade that ultimately leads to glucocorticoids release, seems to stand out as the molecule that coordinates the cross-talk between the two systems Valentino and Van Bockstaele, The LC-NE network is a major target of CRH Chappell et al.

During stress, CRH is released into the LC, increasing neuronal firing rate and consequently NE release in forebrain targets Valentino et al.

Different structures that coordinate autonomic and limbic processing such as CeA Van Bockstaele et al. Interestingly, CRH release within the LC is regulated by basal levels of corticosteroids as well Valentino and Van Bockstaele, This communication between HPA and LC-NE axis determines the structural basis for emotional arousal, facilitates cognition and promote flexible behavioral responses to stress Cole and Koob, ; Valentino and Van Bockstaele, , since CRH release in the LC during stress facilitates shifting of attention between diverse stimuli Snyder et al.

Therefore, this crosstalk enables organisms to tailor different strategies to coping with constant changing environmental challenges. In fact, epinephrine E and NE are secreted from adrenal medulla Cannon, ; de Kloet et al. The circuitry responsible for these autonomic modulations includes direct projections from PVN, LC and RVLM Iversen et al.

Each pre-ganglionic fiber connects with many post-ganglionic neurons located in one or several pre-spinal ganglia or sympathetic paravertebral nuclei Boron and Boulpaep, Although, there are many efferent pathways of the ANS, only two neurons are necessary to transmit impulses between the CNS to the effector tissue Mccorry, Other pre-ganglionic neurons, which end at the spinal cord, do not make synapses with a post-ganglionic neuron.

For instance, they make synapses directly with chromaffin cells in the adrenal medulla Mccorry, ; Boron and Boulpaep, Thus, these two components increase the capacity of the sympathetic division in influencing body visceral responses Boron and Boulpaep, The sympathetic system activation leads to activation of signaling pathways that evoke changes in blood vessels, glands, visceral organs and smooth muscles Tank and Lee Wong, Pre-ganglionic parasympathetic neurons originate from craniosacral vertebral segments brainstem and sacral spinal cord synapse with post-ganglionic neurons in the terminal nodes located more peripherally, and usually on the wall of the target organs.

Post-parasympathetic ganglionic neurons stimulate the muscarinic and nicotinic receptors present on the membrane of the target cells by releasing acetylcholine Boron and Boulpaep, The effect caused by any of these substances, acetylcholine, norepinephrine and epinephrine, depends on the biochemical properties of the cells and on the receptor distribution in a determined tissue Mccorry, In general, SAM activation is considered to mediate short-term effects, with rapid responses, while the HPA axis activation leads to short and long-term effects Joëls and Baram, ; Tank and Lee Wong, Although, these sympathetic and parasympathetic systems act independently from each other Antunes-Rodrigues et al.

E and NE interact with adrenergic receptors present in cell membranes of smooth muscles and in numerous organs, as well as in neurons widespread in the CNS Mccorry, ; Tank and Lee Wong, These receptors are the G-protein coupled receptors GPCRs , which are homologous to muscarinic receptors, i.

There are two major types of adrenergic receptors; α- adrenergic and β-adrenergic receptors, with their subtypes Langer, ; Guimarães and Moura, ; Dünser and Hasibeder, Their effects include: maintaining alertness, metabolic actions increased glucose via glycogenolysis and gluconeogenesis, lipolysis, increased oxygen consumption and thermogenesis and cardiovascular actions Aires, The central noradrenergic system, specifically the LC is involved in multiple neurochemical circuits, having connections with neuroanatomical structures involved in the stress response, such as the HIPPO, amygdala and temporal neocortex.

Studies indicate an important role of the LC in response to acute stress Myers et al. However, chronic activation of the LC may have a potential role in the development of pathological behaviors related to stress Southwick et al. Thus, the release of NE has central actions, coordinates and modulates autonomic, endocrine and neuroendocrine responses, through extensive brain and spinal cord connections, while direct projections from LC to medial parvocellular division of the PVN Cunningham and Sawchenko, allows the modulation of the HPA axis Armario et al.

On the other hand, the activity of LC itself may be influenced by CRH through afferent projections from amygdala and brainstem nuclei McCall et al.

When an organism faces a threatening stimulus, whether it is psychological or physical, as explained in the previous sections, many brain areas are activated in a coordinated fashion to recruit a complex structure known as hypothalamus, which is composed by many sub nuclei.

As already discussed, among those nuclei is the PVN, which is responsible for eliciting the activation of the HPA axis, one of the main components of the stress response. The PVN synthesizes three different neurochemical compounds that behave either as neurotransmitters or hormones, depending on where they are acting.

These compounds are oxytocin, vasopressin and CRH Vale et al. The pituitary is situated caudally and above the optical chiasm, and consists of an anterior portion adenohypophysis , that synthesizes and secretes hormones and of a posterior portion neuro-hypophysis , that stores oxytocin and vasopressin synthesized by the parvocellular neurons in the PVN McCann and Brobeck, ; Joëls and Baram, When CRH reaches the anterior pituitary, it stimulates the corticotrophs to synthesize and release the ACTH Vale et al.

ACTH is secreted through the hypophyseal portal system, and acts on the cortex of the adrenal gland, more specifically on the middle layer named fascicullata Vale et al.

The main glucocorticoid in humans is cortisol, and its equivalent in rodents is corticosterone de Kloet, Although the HPA axis has an ultradian rhythm Young et al. There are many evidences indicating that the suprachiasmatic nucleus SCN of the hypothalamus is the generator of the circadian rhythm Welsh et al.

Glucocorticoids act on the anterior pituitary, PVN and other brain structures, such as the HIPPO McEwen et al. This phenomenon is called short and long negative feedback loops, respectively de Kloet et al.

Glucocorticoids are steroids and easily trespass cell membranes and since they are released in the bloodstream they can virtually reach any cell in the body. Although peripherally the glucocorticoids act massively in several target-organs, here we focus on their effects on the brain.

Cortisol, or corticosterone in rodents, exerts their effects in the brain by binding to two types of receptors, the glucocorticoid receptor GR and the mineralocorticoid receptor MR; Reul and de Kloet, ; de Kloet et al.

These receptors mediate the effects of glucocorticoids in the brain through genomic and non-genomic mechanisms Verkuyl et al. The MR shows 10 times higher affinity for corticosterone than GR Reul and de Kloet, Such difference is translated to receptor occupancy throughout the day, during the through phase of the circadian cycle, when glucocorticoid levels are low, MRs are occupied whereas the GRs are mostly free.

During the peak phase of the circadian cycle, or after high glucocorticoid release due to the stress response, MRs are completely occupied while GRs are partially occupied Kitchener et al. Although glucocorticoids are able to reach all neurons in the brain, they exert effects on those neurons expressing GRs and MRs.

GRs are abundant and widely spread throughout the brain. On the other hand, MRs are expressed in restricted areas of the brain Reul and de Kloet, It is also important to mention that there are some key structures that express both receptors, such as the PVN, HIPPO, amygdala, lateral septum, LC and NTS, among others.

Moreover, GR and MR also co-localize with adrenoreceptors allowing the interplay between the SAM and HPA axes Härfstrand et al. These delayed and long-lasting effects of GR and MR receptor activation Joëls et al.

Moreover, it has also been shown that not only genomic processes are triggered by GR and MR, actually there are studies clearly showing rapid effects of membrane-located MR and GR activation Borski, ; Johnson et al.

Important to mention, it has been demonstrated that GR levels, and consequently HPA axis function, can be modulated by the environment, as well as life experiences acute and chronic stressors , through stable changes in the DNA chromatin, which does not alter DNA sequence, a mechanism known as epigenetics Hunter et al.

Alterations such as methylation and acetylation of histones occur genomewide enhancing or hampering chromatin activity, however DNA methylation can also occur in a gene-specific fashion altering its expression Tsankova et al.

In fact, Weaver et al. These authors demonstrated that pups, which received low care licking and grooming the pups from their dams, had higher hippocampal NC3R1 methylation associated with lower GR expression, when compared to those that received high levels of licking and grooming.

Epigenetic modulation of GR expression has also been described in humans as highlighted by Palma-Gudiel et al. In the other hand, pre-clinical data have associated stress-induced epigenetic alterations with vulnerability or resilience to psychiatry-like conditions Covington et al. Although, the discovery of the interplay between the inflammatory and endocrine systems is dated as a long-time story, it still remains as a hot topic in the field of stress research.

At the same period Hans Selye discovered his canonical findings on stress, the prestigious Mayo Clinique developed the substance E Neeck, ; Hillier, ; Lupien, This substance crystalized by Dr.

Kendall Mason et al. Most recently, research on the relationship between stress hormones and immune system has unraveled many intricate pathways that also can be explored for their clinical implications. It has been postulated that besides preparing the body to deal with the environment demands, stress activates the immune system, which engages active defense against physical injury and pathogens.

Ultimately, cytokines are produced to promote multiple kinds of inflammatory responses Takahashi et al. But reports stated that stress-enhanced inflammatory activity is present in the absence of infectious pathogens, especially in depressed patients Audet et al.

To address whether stress or its hormones are pro or anti-inflammatory, evidence using rodent models demonstrated that stress itself can be both pro- and anti-inflammatory. Some authors have proposed that the timing of immune challenges and measurements determines the direction of glucocorticoid actions.

Those authors proposed that glucocorticoids initially present anti-inflammatory action, but later on sensitizes the immune response on the recovery phase after stressor; Frank et al.

Stress can directly influence immune signaling in two main ways, by reducing the inhibitory effects of glucocorticoid actions, or by directly stimulating the immune system via HPA axis and SAM Liu et al. But not only the neural components of stress engage the immune system, the immune system also affects the CNS, modulating the HPA axis Berkenbosch et al.

Therefore, acutely, stressful experiences enhanced levels of circulatory pro-inflammatory cytokines Steptoe et al. Some of these inflammatory cytokines are either locally produced by activated microglia Wohleb et al.

Interestingly, the sites that have increased pro-inflammatory immune reactivity appear to be related to acute stressor modalities. Social stressors increased expression of pro-inflammatory interleukins and activated microglia in sites such as PFC, amygdala and HIPPO Audet et al.

Stress mediators operate in a feedback loop after HPA axis activation, and regulate, in a positive or negative way, different brain structures to restore homeostasis de Kloet et al. When the timing of stress response is inappropriate, aberrant HPA axis activity could lead to pathological states Heim et al.

We can divide basal regulation of glucocorticoids release in ultradian and circadian cycles, and also categorize the effects of stress response in rapid or delayed regarding their initiation, and in short or long-term, regarding their duration, in both scenarios they range from milliseconds to days Joëls et al.

Moreover, stress also differs when it occurs in early-life or adulthood of an individual, which can increase or decrease the possibility of developing brain disorders Lupien et al.

In ultradian and circadian cycles, peaks of corticosterone release contribute to regulation of basal metabolic demand and the responsiveness of stress Lightman and Conway-Campbell, The origin of pulsatile corticosterone release in an ultradian and circadian fashion is not fully elucidated, but it has been a general assumption that the hypothalamus modulates this phenomenon, specifically, the hypothalamic SCN has efferent projections to neuroendocrine cells in the PVN that trigger the HPA axis activation Engeland and Arnhold, Acute stress mediators start acting within seconds after the stressor detection and provide quick responses to an appropriated strategy, involving modulation of limbic-cortical circuits Bains et al.

After corticosterone is released, frequency of miniature excitatory postsynaptic currents mEPSCs in PVN are suppressed, which decreases glutamatergic excitability and increases GABA inhibition Di et al.

These effects of corticosterone in the PVN occur mainly via non-genomic GR activity and endocannabinoid signaling Di et al. However, in other structures, excitatory activity is increased after acute stress Joëls et al. Similarly, mEPSC frequency in BLA is also increased via MR after acute corticosterone release Karst et al.

Interestingly, firing frequency of BLA neurons remains at high levels even after corticosterone washout, mainly modulated by GR and cannabinoid receptor 1 Karst et al.

In cortical structures, such as the PFC, acute stress situation increases GR-dependent glutamate release Musazzi et al. Hours after stressor exposure, delayed effects start to occur in a different way on limbic-cortical structures Joëls et al.

Neurons of CA1 have enhanced amplitude but not frequency of mEPSCs via GR Karst et al. The GR activity also modulates synaptic plasticity in CA1, promoting Long-term Depression LTD and impairs Long-term Potentiation LTP; Pavlides et al.

In opposite, corticosterone presents delayed effects via MR by increasing the induction of LTP in CA1 Pavlides et al. In BLA, delayed effects of corticosterone increase excitability of neurons, maintaining excitability after acute stress Duvarci and Paré, Similarly, corticosterone enhances glutamatergic transmission and reduces inhibitory post-synaptic currents mIPSCs in the PFC Hill et al.

These delayed effects of stress in limbic-cortical structures restore homeostasis, as well as retain important information to better cope with similar situations in the future Joëls et al.

When there is an over-exposure to stressors, lasting from hours to days, it is possible to observe structural changes in limbic-cortical areas and even in the reward system Joëls et al. Dendritic complexity is progressively reduced in HIPPO and PFC, after chronic exposure to stressors McEwen and Magarinos, ; Holmes and Wellman, By contrast, neurons in the BLA and NAc increase dendritic density, increase excitatory tone and decrease inhibitory tone in this context Vyas et al.

At the cellular level, chronic stress impairs induction of LTP in CA1 of the HIPPO and reduces both AMPA and NMDA-mediated synaptic transmission Joëls et al. The behavioral consequences of these structural changes were associated with anxious behavior, probably by hypertrophy of the amygdala Mitra and Sapolsky, and deficits in learning, which could be explained by impaired hippocampal and PFC structures Joëls et al.

It is interesting to note that when chronic stress is experienced early in life, its effects on the brain last longer than when it occurs during adulthood Lupien et al. When rodent pups are exposed to prolonged maternal separation, the density of CRH binding sites increases in HIPPO, amygdala and PFC Anisman et al.

Activity of CRH mediates stress-related synaptic plasticity loss in the HIPPO, anxiogenic behavior dependent of amygdala and cognitive impairment associated with PFC Schulkin et al. At this point, in our evolutionary history, stress could be implied in a maladaptive performance in a large proportion of the population, considering the large number of comorbidities that occur from dysfunction of the stress system de Kloet et al.

The HPA axis dysregulation and prolonged exposure to glucocorticoids reduce the ability of neurons to resist insults, increasing the risk for injury by other toxic events Lupien et al. Moreover, new researches have called attention to adversities in early life, which are greatly associated with higher vulnerability to disorders later in life, causing a long-term impact in the circuitry responsible for cognitive and emotional function Gold et al.

In this sense, both basic and clinical researches have advanced in recent years but much remains to be understood about the subject. In general, animal models have provided a comprehensive view of the stress effects on the brain, abundantly on the limbic structures Hariri and Holmes, The amygdala is a highly conserved brain structure that is fundamental to detect potential danger Janak and Tye, , while HIPPO provides support to encoding environmental information associated with the stressor Herman et al.

The identification of these highly evolutionary conserved networks that are affected by stress, allowed important discoveries in clinical research Hariri and Holmes, Increasing data highlight that highly debilitating stress comorbidities such as depression, anxiety disorders, PTSD and epilepsy share pathogenic mechanisms with stress dysfunction and between each other.

These mechanisms are probably deeply connected and the structural and functional change caused by one disease triggers the other, despite these it is still not clear on the relationship between them Gold et al. Considering this, we presented in this review a short glimpse of how stress is related to these CNS pathologies.

For further review, we suggest to look into the literature cited here. A significant percentage of patients with Major Depression MD have increased concentrations of cortisol in plasma, urine and cerebrospinal fluid, exaggerated cortisol response after ACTH hormone stimulation and hyperplasia of the pituitary and adrenal glands Gold et al.

Chronic stressors in early life result in permanent epigenetic, endocrine, neural, immune and inflammatory changes, constituting a relevant risk factor for several neuropsychiatric diseases in adult life Xiong and Zhang, ; Zhang et al. In epilepsy, stress can influence in multiple ways, often as seizure-precipitating but also increased the risk of epilepsy development van Campen et al.

However, studies indicate that infancy coincides with a period referred as hyporesponsive period to stress Stress Hyporesponsive Period—SHRP , which is supposed to be a period that is necessary for the proper development of the brain after birth Sapolsky and Meaney, ; de Kloet et al.

It corresponds with a period of low peripheral concentration of glucocorticoids, in which a physiological response to mild stress increased glucocorticoids and adrenaline, increased cardiovascular circulation, immune system modifications does not occur.

There is no consensus when exactly this period starts or how long it lasts, but it is suggested that it could last from around the 2nd to 12th postnatal day in rodents Sapolsky and Meaney, and up to 5 years in humans Gunnar and Donzella, ; Curley et al. Interestingly, psychological Sapolsky and Meaney, and multimodal stressors Godoy et al.

The effects of stress during early life ELS on the brain have been deeply studied for review see Lupien et al. ELS disrupts the proper development and function of limbic structures, leading to lifelong susceptibility to stress on behavior and cognition as well as on the reward system Peña et al.

More recently it has been demonstrated that ELS led to an early emergence of timed developmental suppression of fear behavior that correlates to an early maturation Bath et al. Depression-anxiety comorbidity is strongly associated with impairment in health, as well as in cognitive and emotional functions Kroenke et al.

Similarly, chronic treatment with corticosterone not only generates depressive-like symptoms but also induces amygdala hypertrophy and increases anxiogenic behavioral responses Mitra and Sapolsky, In humans, individual differences in amygdala reactivity to threat-related facial expressions predict vulnerability to stress, such as subjects with hyperactivation of the amygdala are more likely to experience depression and anxiety symptoms Yang et al.

Also, hyperactivation of LC-NE is related to neuropsychiatric disorders such as PTSD and MD, the activation of this system out of proper context may lead to hyperarousal, loss of concentration, restlessness and impaired focused attention, which are characteristic symptoms of stress-related psychiatric disorders Southwick et al.

For instance, PTSD is associated with increased rates of anxiety and depression Nemeroff et al. However, some clinical investigations reported low levels of cortisol in PTSD patients, while individuals with anxiety disorders or depression show an increase of cortisol response Daskalakis et al.

Actually, the literature reports alterations in the HPA axis in PTSD patients and from the study by Mason et al. However, there are studies also showing no differences Baker et al. Because this topic remains controversial in the literature, more insights such as those presented in Zoladz and Diamond are recommended.

Alterations in other compartments of the HPA axis were also identified in PTSD patients such as enhanced GR sensitivity and HPA axis enhanced negative feedback Grossman et al. Animal models of PTSD can directly address these questions, but it is known that different types of aversive exposure in PTSD models e.

Actually, exposure to severe stressors such as urban violence, sexual abuse, combat in war, disasters and many others, is believed to be associated to development of PTSD, leading individuals to present physiological and behavioral alterations including nightmares, hypervigilance, flashbacks of the trauma and sleep disturbances DSM-V, Zoladz and Diamond, ; Yehuda et al.

Although a positive correlation has been reported between the severity of the trauma and PTSD symptomatology in veteran soldiers Snow et al. It has also been reported that the type of stressor seems to play a bigger role than its severity Kessler et al.

Interestingly, not everybody develops PTSD after trauma exposure, which suggests that other factors despite the trauma severity and type , such as socioeconomic profile, psychiatry disorder history, substance abuse, immune system, genetics and epigenetics play a role on the susceptibility for PTSD.

Actually, there are evidences showing that the interplay between environment and genetics and epigenetics are risk factors for PTSD development Mehta and Binder, ; Wilker and Kolassa, ; DiGangi et al. In patients with epilepsy, stress is usually reported as one of the major seizure precipitants Frucht et al.

In adults, there is a positive correlation between stress and frequency of epileptic seizures Swinkels et al. Epileptogenesis is a multi-stage process that can begin early in life and may be negatively influenced by stress Joëls, , and it is now suggested that early life stress can create permanent vulnerability to the development of epilepsy Huang, Therefore, many evidences indicate that stress is relevant in the phases of epileptogenesis, both in adults and young people.

Corticosterone plays a contributory role in the epileptogenic process in animal models of epilepsy Karst et al. This could occur indirectly through the genomic effects of glucocorticoids, resulting in alterations of networks associated with seizures, or by direct non-genomic effects of these on the excitability of the limbic system Joëls, Other pathologies affect the peripheral nervous system and many different organs.

The CRH circuitry connecting LC-NE and PVN is strategically positioned so it may control autonomic responses to visceral stimuli and may underlie the co-morbidity of pelvic visceral and behavioral symptoms observed in many stress-related disorders Valentino et al.

Although most immediate responses coordinated by SAM axis are important for survival, when levels of circulating catecholamines are maintained elevated for prolonged periods of time, they can lead to different pathologies.

In the past decades identification of neuronal circuits associated to stress, as well as their interaction with mediators over time, was critical not only for understanding physiological stress responses, but also to understand their clinical implications. Stress-related brain disorders are extremely prevalent, so identification of mechanisms related to stress and consequently the potential development of new pharmacological therapeutic approaches are necessary and urgent.

As an example, pre-clinical studies on psychopathology-related topics are being done with classic GR antagonist RU Arp et al. These compounds are the so-called selective glucocorticoid receptor modulators SGRMs which upon binding to the GR promote a differential conformation of the receptor leading to differential recruitment of corregulators and therefore enhancing or hampering gene expression in a cell-tissue specific manner.

Thus, the same compound can induce agonist- and antagonist-like effects, for instance the SGRMs C acts as an antagonist in neurogenesis related processes such as proliferation and survival of hippocampal neurons, and as an agonist in fear memory retention on the avoidance behavior task Zalachoras et al.

In the other hand the C compound acts as an antagonist in the same task whereas showing agonist effects on plasmatic corticosterone levels Atucha et al. From our own experience the Wistar Audiogenic Rat WAR strain is a genetically selected experimental epilepsy model, which displays after 56 generations of inbreeding, not only seizure-associated behaviors and electrophysiological alterations, but also comorbidities which includes high anxiety, hyperactive HPA axis, adrenal medulla hyperplasia, ectopic beats, high blood pressure, tachychardia and central respiratory alterations Fazan et al.

Further experiments are therefore needed in order to evaluate the pharmacological profile of new anti-epileptic, anxiolytic or even anti-depressive drugs, using as a model of comorbidities of the WAR strain.

In the clinical scenario a final comment can be done, when referring to the additional complexity associated, for example, to the presence of comorbid neurological and neuropsychiatric conditions, such as, for example, the epilepsies, autism and mood disorders, recognizing that we are talking about network disorders Kanner et al.

In the particular case of depression, anxiety and epilepsy, Kanner and Nogueira et al. Therefore stressors, which work as triggers, such as those cited in the current review, are common to all the situations.

On the other hand, Rayner highlights that complex cognitive networks associated to depression interact so strongly with epilepsy related networks, in a way that the difficulties with diagnosis and treatment increase, as soon as we recognize that those networks share common structures and mechanisms.

One way to overcome this, in order to make relevant and reliable contributions in this field, is the construction of algorhythms from computational neuroscience modeling, where actual data, either from basic science or from human clinical settings are used to generate predictions with translational value.

In that context, recently Spiga et al. inflammatory stress. In brief, these authors showed in a rat model, that although the steroidogenic regulatory network architecture is sufficient to respond to both small and large ACTH perturbations, coupling the regulatory network with the immune system would explain dissociated dynamics between ACTH and glucocorticoids observed when inflammatory stress is present.

We are able to adapt to the dynamic and challenging environment we live in, as well as to unexpected life events we face every now and then.

Examples are endless and, most of the time, we can overcome these events. We are able to do so because the existence of quite complex networks, which integrate body and brain, in order to enhance performance, promote adaptation and ultimately survival, the stress system.

A diversity of brain areas integrates sensorial, physiological and emotional signs. When different brain networks interpret these signs as a threat real or potential , a series of responses follow, increasing performance to deal with the situation and retain that information to better cope with similar situations in the future, characterizing the stress response.

The downside of the stress system is that sometimes it is not able to overcome the environmental, physiological or emotional demand. The aim of this review article was to bring comprehensive basic concepts about the stress system such as history of stress research, neuroanatomy, major effectors of the stress response, time domains of stress and the clinical implication of malfunction might have over the susceptibility to the development of increasingly-common brapdin disorders.

LDG, MTR and PD-P wrote the manuscript draft. NG-C and EHLU conceptualize, wrote and corrected the manuscript. LDG and MTR contributed equally to this work.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We would like to thank all students enrolled in the Course on Behavioural, Neuro-Psychopharmacological, Endocrine and Molecular Aspects of Stress RFI held at the Graduate Program in Physiology PROEX-CAPES of the FMRP-USP in July , who contributed with insightful discussions.

To the Course Staff Marian Joëls, Ron de Kloet, Mário Juruena, Marcus Brandão, Samia Joca and Cristiane Baes for their inspirational lectures. Abercrombie, E. Differential effect of stress on in vivo dopamine release in striatum, nucleus accumbens, and medial frontal cortex.

doi: PubMed Abstract CrossRef Full Text Google Scholar. Aires, M. Rio de Janeiro: Guanabara-Koogan. Alt, S. Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed. Psychoneuroendocrinology 35, — Amaral, D. The three-dimensional organization of the hippocampal formation: a review of anatomical data.

Neuroscience 31, — Amir, M. Type of trauma, severity of posttraumatic stress disorder core symptoms, and sssociated features. Andersen, P. The hippocampal lamella hypothesis revisited. Brain Res. Angeli, A.

Modulation by cytokines of glucocorticoid action. N Y Acad. Anisman, H. Do early-life events permantently alter behavior and hormonal responses to stressors? Antunes-Rodrigues, J. Neuroendocrinologia: Básica e Aplicada. Rio de Janeiro: Guanabra-Koogan.

Armario, A. What can we know from pituitary-adrenal hormones about the nature and consequences of exposure to emotional stressors? Arnsten, A. Stress signaling pathways that impair prefrontal cortex structure and function.

Arp, J. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress. Atucha, E.

Endocrinology , — Audet, M. Social defeat promotes specific cytokine variations within the prefrontal cortex upon subsequent aggressive or endotoxin challenges. Brain Behav. Behavior and pro-inflammatory cytokine variations among submissive and dominant mice engaged in aggressive encounters: moderation by corticosterone reactivity.

Cytokine variations and mood disorders: influence of social stressors and social support. Bagot, R. Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression.

Bains, J. Stress-related synaptic plasticity in the hypothalamus. Baker, D. Serial CSF corticotropin-releasing hormone levels and adrenocortical activity in combat veterans with posttraumatic stress disorder. Psychiatry , — PubMed Abstract Google Scholar. Banks, W. The blood-brain barrier in psychoneuroimmunology.

Barbas, H. Topographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey. Hippocampus 5, — Başoglu, M. Factors related to long-term traumatic stress responses in survivors of torture in Turkey.

JAMA , — Bassareo, V. Differential expression of motivational stimulus properties by dopamine in nucleus accumbens shell versus core and prefrontal cortex. Bath, K. Studies have shown that cooler temperatures can help to reduce stress levels and improve cognitive functioning.

In addition, the filtered air provided by an air conditioner can help to reduce exposure to allergens and other airborne contaminants, creating a healthier atmosphere.

And because air conditioners help to improve indoor air quality, they can also reduce headaches, nausea, and fatigue. In short, air conditioners can have a profound impact on our physical and mental well-being.

As such, they should be properly maintained and regularly serviced in order to ensure that they are operating at peak efficiency. Air conditioners can play an important role in reducing odors and fumes in your home. By circulating air, they help to reduce the concentration of airborne particles, including odorous molecules.

In addition, air conditioners help to remove humidity from the air, which can further reduce the intensity of smells.

While air conditioners cannot completely eliminate all odors and fumes, they can significantly reduce their levels, making your home more pleasant and comfortable. Dehydration is a serious health risk that can lead to a number of complications.

While dehydration is often associated with strenuous exercise or hot weather, it can also occur when the body is unable to regulate its internal temperature. This can happen during a fever, for example, or when exposed to extremely cold temperatures.

Air conditioners can help to reduce the risk of dehydration by maintaining a comfortable temperature indoors. This prevents the body from overheating and sweating excessively, which can lead to dehydration. As a result, air conditioners can play an important role in preventing dehydration.

Air conditioners are a staple in many homes during the summertime. Not only do they keep us cool, but they also improve our health and well-being. Please leave this field empty. Skip to content How Air Conditioners Help Your Health and Well-Being. Contact Us Proudly Serving Evansville.

Genomic and archaeological evidence suggest a dual origin of domestic dogs. aaf Article ADS CAS PubMed Google Scholar. Buttner, A. Evidence for a synchronization of hormonal states between humans and dogs during competition.

Article CAS Google Scholar. Hellhammer, D. Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology 34 , — Heimbürge, S.

The use of hair cortisol for the assessment of stress in animals. Article CAS PubMed Google Scholar. Ouellette, S. Hair cortisol concentrations in higher- and lower-stress mother-daughter dyads: A pilot study of associations and moderators.

Schloss, S. Neural Transm. Marshall-Pescini, S. The effect of training and breed group on problem-solving behaviours in dogs.

Animal cogn. Roth, L. Hair cortisol varies with season and lifestyle and relates to human interactions in German shepherd dogs. Article ADS CAS PubMed PubMed Central Google Scholar. Meyer, I. Dog and owner characteristics affecting the dog—owner relationship.

Schöberl, I. Psychobiological Factors Affecting Cortisol Variability in Human-Dog Dyads. Article CAS PubMed PubMed Central Google Scholar.

Gerber, M. Concerns regarding hair cortisol as a biomarker of chronic stress in exercise and sport science. Sports Sci. PubMed PubMed Central Google Scholar. Baron-Cohen, S. Sex differences in the brain: implications for explaining autism.

Romero, T. Consolation as possible expression of sympathetic concern among chimpanzees. Article ADS PubMed Google Scholar. Bartal, I. Empathy and Pro-Social Behavior in Rats. Article ADS CAS PubMed Central Google Scholar.

Christov-Moore, L. Empathy: gender effects in brain and behavior. Nagasawa, M. Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds. Kotrschal, K. Dyadic relationships and operational performance of male and female owners and their male dogs.

Processes 81 , — De Palma, C. Evaluating the temperament in shelter dogs. Behaviour , — Ottenheimer Carrier, L. Exploring the dog park: Relationships between social behaviours, personality and cortisol in companion dogs.

Beetz, A. Psychosocial and psychophysiological effects of human-animal interactions: the possible role of oxytocin. Article PubMed PubMed Central Google Scholar.

Mubanga, M. Dog ownership and the risk of cardiovascular disease and death — a nationwide cohort study. Polheber, J. The presence of a dog attenuates cortisol and heart rate in the Trier Social Stress Test compared to human friends. Rehn, T. Evaluating the Strange Situation Procedure SSP to Assess the Bond between Dogs and Humans.

MacLean, E. Effects of Affiliative Human—Animal Interaction on Dog Salivary and Plasma Oxytocin and Vasopressin. Jones, A. Development and validation of a dog personality questionnaire Zakrisson, I. Big Five Inventory BFI [Elektronisk resurs]: Utprövning för svenska förhållanden.

Mittuniversitetet, Karlén, J. Cortisol in hair measured in young adults-a biomarker of major life stressors? BMC Clin. Download references. We are very grateful to the devoted dog owners who participated in this study.

IFM Biology, AVIAN Behavioural Genomics and Physiology group, Linköping University, 83, Linköping, Sweden. Department of Medical and Health Sciences, Linköping University, 85, Linköping, Sweden.

Department of Clinical and Experimental Medicine, Linköping University, 85, Linköping, Sweden. You can also search for this author in PubMed Google Scholar. The study was initiated and designed by L.

and A. The analyzation in the lab was performed by E. with help from A. and E. The statistical analysis and the figures were performed by A. and L. wrote the manuscript while all authors reviewed and approved the final version of the article submitted for publication.

Correspondence to Lina S. Open Access This article is licensed under a Creative Commons Attribution 4. Reprints and permissions. Sundman, AS. Long-term stress levels are synchronized in dogs and their owners. Sci Rep 9 , Download citation. Received : 25 January Accepted : 02 May Published : 06 June Anyone you share the following link with will be able to read this content:.

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Nurturing yourself is a necessity, not a luxury. If you regularly make time for fun and relaxation, you'll be in a better place to handle life's stressors.

Set aside leisure time. Include rest and relaxation in your daily schedule. This is your time to take a break from all responsibilities and recharge your batteries.

Do something you enjoy every day. Make time for leisure activities that bring you joy, whether it be stargazing, playing the piano, or working on your bike. Keep your sense of humor. This includes the ability to laugh at yourself. The act of laughing helps your body fight stress in a number of ways.

Take up a relaxation practice. Relaxation techniques such as yoga, meditation, and deep breathing activate the body's relaxation response , a state of restfulness that is the opposite of the fight or flight or mobilization stress response. As you learn and practice these techniques, your stress levels will decrease and your mind and body will become calm and centered.

Poor time management can cause a lot of stress. When you're stretched too thin and running behind, it's hard to stay calm and focused. Plus, you'll be tempted to avoid or cut back on all the healthy things you should be doing to keep stress in check, like socializing and getting enough sleep.

The good news: there are things you can do to achieve a healthier work-life balance. Don't over-commit yourself. Avoid scheduling things back-to-back or trying to fit too much into one day.

All too often, we underestimate how long things will take. Prioritize tasks. Make a list of tasks you have to do, and tackle them in order of importance.

Do the high-priority items first. If you have something particularly unpleasant or stressful to do, get it over with early. The rest of your day will be more pleasant as a result. Break projects into small steps. If a large project seems overwhelming, make a step-by-step plan.

Focus on one manageable step at a time, rather than taking on everything at once. Delegate responsibility. You don't have to do it all yourself, whether at home, school, or on the job. If other people can take care of the task, why not let them? Let go of the desire to control or oversee every little step.

You'll be letting go of unnecessary stress in the process. In addition to regular exercise, there are other healthy lifestyle choices that can increase your resistance to stress. Eat a healthy diet. Well-nourished bodies are better prepared to cope with stress, so be mindful of what you eat.

Start your day right with breakfast, and keep your energy up and your mind clear with balanced, nutritious meals throughout the day. Reduce caffeine and sugar. Avoid alcohol, cigarettes, and drugs. Self-medicating with alcohol or drugs may provide an easy escape from stress, but the relief is only temporary.

Get enough sleep. Adequate sleep fuels your mind, as well as your body. Feeling tired will increase your stress because it may cause you to think irrationally.

When you're frazzled by your morning commute, stuck in a stressful meeting at work, or fried from another argument with your spouse, you need a way to manage your stress levels right now.

That's where quick stress relief comes in. The fastest way to reduce stress is by taking a deep breath and using your senses—what you see, hear, taste, and touch—or through a soothing movement.

By viewing a favorite photo, smelling a specific scent, listening to a favorite piece of music, tasting a piece of gum, or hugging a pet, for example, you can quickly relax and focus yourself. Of course, not everyone responds to each sensory experience in the same way.

The key to quick stress relief is to experiment and discover the unique sensory experiences that work best for you.

The power of the relaxation response to reduce stress and boost mood. Using close relationships to manage stress and improve well-being. BetterHelp makes starting therapy easy. Take the assessment and get matched with a professional, licensed therapist. Millions of readers rely on HelpGuide.

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About Us Meet Our Team Our Story Jeanne Segal, Ph. Harvard Health Partnership Audio Meditations Newsletter. What is stress management? Copy Link Link copied! Download PDF. By Lawrence Robinson and Melinda Smith, M. Tip 1: Identify the sources of stress in your life Tip 2: Cut out unhealthy ways of dealing with stress Tip 3: Practice the 4 A's of stress management Tip 4: Get moving Tip 5: Connect to others Tip 6: Make time for fun and relaxation Tip 7: Manage your time better Tip 8: Maintain balance with a healthy lifestyle Tip 9: Learn to relieve stress in the moment.

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Harvard Health Tolerating Distress - Workbook and information sheets to help you manage feelings of distress. Centre for Clinical Interventions Building Your Resilience - Learn how to increase your resilience in the face of stress and hardship.

American Psychological Association How To Relax: 8 Relaxation Tips for Your Mental Health. Trauma- and Stressor-Related Disorders. In Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association. Can, Yekta Said, Heather Iles-Smith, Niaz Chalabianloo, Deniz Ekiz, Javier Fernández-Álvarez, Claudia Repetto, Giuseppe Riva, and Cem Ersoy.

Norelli, Samantha K. Treasure Island FL : StatPearls Publishing, Toussaint, Loren, Quang Anh Nguyen, Claire Roettger, Kiara Dixon, Martin Offenbächer, Niko Kohls, Jameson Hirsch, and Fuschia Sirois. Unger, Cynthia A, David Busse, and Ilona S Yim.

Singh, Karuna. Katsarou, Alexia L. Vryonis, Athanassios D. Protogerou, Evangelos C. Alexopoulos, Apostolos Achimastos, Dimitrios Papadogiannis, George P. Chrousos, and Christina Darviri. Errisuriz, Vanessa L. Pasch, and Cheryl L.

Choi, Dong-Woo, Sung-Youn Chun, Sang Ah Lee, Kyu-Tae Han, and Eun-Cheol Park. Blaxton, Jessica M. Bergeman, Brenda R. Whitehead, Marcia E. Braun, and Jessic D. Saleh, Dalia, Nathalie Camart, Fouad Sbeira, and Lucia Romo. A Randomized Controlled Trial Carried out on University Students.

Loprinzi, Paul D. Salmon, P. More in Stress Stress Relaxation Techniques for Stress Relief The power of the relaxation response to reduce stress and boost mood 14 mins. Stress Quick Stress Relief Using your senses to relieve stress on the spot 12 mins.

Anxiety How to Stop Worrying Self-help strategies for anxiety relief 17 mins. Stress Social Support for Stress Relief Using close relationships to manage stress and improve well-being 17 mins. Stress 12 Ways to Reduce Stress with Music Fill your life with music that reduces daily stress 10 mins.

Too much humidity can lead to the growth of mold and mildew, which can trigger allergies. By keeping humidity levels under control, air conditioners can create a more allergy-friendly environment.

In many office settings, the working conditions can be less than ideal. The temperature may be too hot or too cold, the lighting may be harsh or fluorescent, and the noise level may be too high. These conditions can lead to a decrease in concentration and productivity.

However, by using an air conditioner, you can create a more comfortable work environment that is conducive to concentration and productivity. Air conditioners help to regulate the temperature, filter out harmful airborne particles, and reduce background noise.

As a result, they can have a positive impact on your ability to get work done. If you are looking for ways to boost your productivity, investing in an air conditioner is a good place to start. While air conditioners are most commonly associated with providing relief from the heat, they can also serve an important role in protecting your health.

First, by keeping the air inside your home cool and dry, air conditioners create an environment that is unfavorable for many insects and parasites. Second, by circulating the air inside your home, air conditioners can help to keep away mosquitos and other flying insects that might carry diseases.

Finally, air conditioners can also help to control the temperature of your home, making it less hospitable for insects and parasites that thrive in warm environments.

In the summer months, the heat can be unbearable. Air conditioners provide relief from the oppressive heat and improve your sleep. The cool air is refreshing and can help you to feel more comfortable and relaxed. Sleeping in a cool, comfortable environment is essential for your well-being and can help you to get the rest you need.

Air conditioners can also improve the indoor air quality of your home by filtering out dust and pollen. As a result, they not only provide relief from the summer heat but also improve your overall health and comfort.

Air conditioners not only improve the quality of the air we breathe, but they can also have a positive effect on our stress levels and moods.

Studies have shown that cooler temperatures can help to reduce stress levels and improve cognitive functioning.

In addition, the filtered air provided by an air conditioner can help to reduce exposure to allergens and other airborne contaminants, creating a healthier atmosphere. And because air conditioners help to improve indoor air quality, they can also reduce headaches, nausea, and fatigue. In short, air conditioners can have a profound impact on our physical and mental well-being.

As such, they should be properly maintained and regularly serviced in order to ensure that they are operating at peak efficiency. Air conditioners can play an important role in reducing odors and fumes in your home.

By circulating air, they help to reduce the concentration of airborne particles, including odorous molecules. In addition, air conditioners help to remove humidity from the air, which can further reduce the intensity of smells. While air conditioners cannot completely eliminate all odors and fumes, they can significantly reduce their levels, making your home more pleasant and comfortable.

Dehydration is a serious health risk that can lead to a number of complications. While dehydration is often associated with strenuous exercise or hot weather, it can also occur when the body is unable to regulate its internal temperature.

Ouellette, S. Hair cortisol concentrations in higher- and lower-stress mother-daughter dyads: A pilot study of associations and moderators. Schloss, S. Neural Transm. Marshall-Pescini, S. The effect of training and breed group on problem-solving behaviours in dogs.

Animal cogn. Roth, L. Hair cortisol varies with season and lifestyle and relates to human interactions in German shepherd dogs. Article ADS CAS PubMed PubMed Central Google Scholar. Meyer, I. Dog and owner characteristics affecting the dog—owner relationship.

Schöberl, I. Psychobiological Factors Affecting Cortisol Variability in Human-Dog Dyads. Article CAS PubMed PubMed Central Google Scholar. Gerber, M. Concerns regarding hair cortisol as a biomarker of chronic stress in exercise and sport science.

Sports Sci. PubMed PubMed Central Google Scholar. Baron-Cohen, S. Sex differences in the brain: implications for explaining autism. Romero, T. Consolation as possible expression of sympathetic concern among chimpanzees. Article ADS PubMed Google Scholar. Bartal, I. Empathy and Pro-Social Behavior in Rats.

Article ADS CAS PubMed Central Google Scholar. Christov-Moore, L. Empathy: gender effects in brain and behavior. Nagasawa, M. Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds.

Kotrschal, K. Dyadic relationships and operational performance of male and female owners and their male dogs. Processes 81 , — De Palma, C. Evaluating the temperament in shelter dogs. Behaviour , — Ottenheimer Carrier, L. Exploring the dog park: Relationships between social behaviours, personality and cortisol in companion dogs.

Beetz, A. Psychosocial and psychophysiological effects of human-animal interactions: the possible role of oxytocin. Article PubMed PubMed Central Google Scholar. Mubanga, M.

Dog ownership and the risk of cardiovascular disease and death — a nationwide cohort study. Polheber, J. The presence of a dog attenuates cortisol and heart rate in the Trier Social Stress Test compared to human friends. Rehn, T. Evaluating the Strange Situation Procedure SSP to Assess the Bond between Dogs and Humans.

MacLean, E. Effects of Affiliative Human—Animal Interaction on Dog Salivary and Plasma Oxytocin and Vasopressin. Jones, A. Development and validation of a dog personality questionnaire Zakrisson, I. Big Five Inventory BFI [Elektronisk resurs]: Utprövning för svenska förhållanden. Mittuniversitetet, Karlén, J.

Cortisol in hair measured in young adults-a biomarker of major life stressors? BMC Clin. Download references. We are very grateful to the devoted dog owners who participated in this study.

IFM Biology, AVIAN Behavioural Genomics and Physiology group, Linköping University, 83, Linköping, Sweden. Department of Medical and Health Sciences, Linköping University, 85, Linköping, Sweden.

Department of Clinical and Experimental Medicine, Linköping University, 85, Linköping, Sweden. You can also search for this author in PubMed Google Scholar. The study was initiated and designed by L. and A.

The analyzation in the lab was performed by E. with help from A. and E. The statistical analysis and the figures were performed by A. and L. wrote the manuscript while all authors reviewed and approved the final version of the article submitted for publication. Correspondence to Lina S. Open Access This article is licensed under a Creative Commons Attribution 4.

Reprints and permissions. Sundman, AS. Long-term stress levels are synchronized in dogs and their owners.

Sci Rep 9 , Download citation. Received : 25 January Accepted : 02 May Published : 06 June Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. By submitting a comment you agree to abide by our Terms and Community Guidelines.

If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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Download PDF. Subjects Animal behaviour Animal physiology. This article has been updated. Abstract This study reveals, for the first time, an interspecific synchronization in long-term stress levels.

Introduction Emotional contagion, the mirroring of emotional or arousal states between individuals, is commonly seen among group-living species 1 , for example as a synchronization of acute stress responses 2 , 3.

Results Effects of human HCC, breed, sex and lifestyle on dog HCC The effect of human HCC on dog HCC was analyzed with a generalized linear model GLM for both winter and summer samples. Figure 1. Full size image. Figure 2. Figure 3. Figure 4. Discussion Through assessment of cortisol concentration in hair of both dogs and their owners, we found an interspecific long-term stress hormone synchronization within the dog-human dyad Fig.

Figure 5. Conclusion Our results show that long-term stress hormone levels were synchronized between dogs and humans, two different species sharing everyday life. Study subjects The participating dyads were recruited through social media and personal contacts and consisted of 33 Shetland sheepdogs 18 females and 15 males and 25 border collies 13 females and 12 males , and their female owners Dataset 1.

Personality and lifestyle surveys Personalities of the dogs and owners were assessed through owner-completed Dog Personality Questionnaire DPQ 32 and Big Five Inventory BFI Change history 08 October An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Article Google Scholar Download references. Acknowledgements We are very grateful to the devoted dog owners who participated in this study. Roth Department of Medical and Health Sciences, Linköping University, 85, Linköping, Sweden Åshild Faresjö Department of Clinical and Experimental Medicine, Linköping University, 85, Linköping, Sweden Elvar Theodorsson Authors Ann-Sofie Sundman View author publications.

View author publications. Ethics declarations Competing Interests The authors declare no competing interests. Supplementary information. Supplementary files. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4. About this article.

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