Stress Hardware Review: The HPA

ScenicSkyway_EN-US2786891862In addition to genetic factors, there are many external factors that influence our individual vulnerability to stress, including childhood trauma, early environmental factors, major life events or physical illness. These factors can influence the intensity and duration of our stress reaction, in many cases producing long-lasting effects. The stress caused by traumatic events may cause chronic stress syndromes such as PTSD, promote the onset of physical disease or worsen existing conditions, including rheumatoid arthritis, chronic pain, fibromyalgia, and multiple sclerosis, among others.

However, while individuals vary greatly in their ability to respond adequately to stressful situations, every human body is programmed and equipped to respond to the initial stressor in the same biochemical way. Among the principal structures that are immediately mobilized in the event of a physical or psychological threat is the hypothalamic-pituitary-adrenal axis (HPA). The HPA consists of three elements connected by blood vessels: the hypothalamus, the pituitary gland, and the adrenal glands. Their functioning depends almost entirely on a sequence of cascading chemical signals.

The HPA Structures and Their Chemical Output

The paraventricular nucleus (PVN) of the hypothalamus is a heterogeneous collection of specialized neurons that, when activated by stress, release corticotrophin releasing hormone(CRH) in the bloodstream. The hippocampus is an important component of the negative-feedback regulation of the neuroendocrine stress response.

PituitaryGlandThe pituitary gland or hypophysis is a very small gland (one-third of an inch in diameter and one twentieth of an ounce in weight) located in a bony cavity at the base of the brain, and connected to the hypothalamus by the pituitary stalk. The pituitary two main components are the neurohypophysis that grows from the floor of the hypothalamus, and the adenohypophysis which releases adrenocorticotropic hormone (ACTH). The hormones released by the pituitary exert strong regulatory control over a wide range of bodily functions, including behavior, growth and development, metabolism, salt and water balance, reproduction and immunity. Stress influences the neuroendocrine regulation of a number of pituitary hormones including ACTH, prolactin, growth hormone, luteinizing hormone, thyrotrophin, vasopressin and oxytocin.

The adrenal glands are located in an area that lies dorsal to the kidney and release the glucocorticoid cortisol or corticosterone.

The HPA’s Starring Role in Stress Regulation

The appropriate functioning of the HPA axis is absolutely vital for species survival in humans and in all vertebrates. The HPA axis functions as a closed-loop system involving tight negative-feedback control regulated by the glucocorticoids. Automatic regulation of the HPA axis is essential for ensuring that the stress reaction is terminated after the stressor subsides, thus preventing continuous excessive activation and a healthy return to internal homeostasis.

How the HPA Responds to Acute and Chronic Stress

Most stressors affecting human life can be classified as either systemic or neurogenic stressors. Systemic stressors include all physical stressors that are a challenge to physical well-being and integrity of the body. Neurogenic stressors include those stressful stimuli that have a predominantly emotional or psychological component, such as fear or anxiety.

Exposure to acute stressors produces an immediate and intense activation of the HPA axis which results in enhanced secretion of ACTH and glucocorticoids. The HPA axis responds to the intensity of each individual stressor, in such a way that repeated or intensified stress results in increased secretion of the stress hormones. Regardless of the type of stimuli that cause an acute stress reaction, the removal of the stressor produces the return of HPA-axis activity to baseline or homeostasis.

In chronic or long-lasting stress, the exact mechanisms that produce long-term activity of the HPA axis and the near-continuous secretion of stress hormones remain largely unknown. However, numerous studies have revealed that the de-activating sequences essential to the maintenance of HPA axis integrity, including negative-feedback control, become dysregulated by prolonged stress stimulation.

Most researchers agree on the hypothesis that a defective over-activation of the HPA axis and the associated excessive secretion of powerful glucocorticoids can cause prolonged suppression of the immune system and dysregulation of immune cells, ultimately predisposing the chronically stressed individual to autoimmune disease. On the other side of the equation, the under-activation of the HPA axis has significant implications for our ability to recognize threats and be able to react to them accordingly.

Stress Hardware Review: Anterior Cingulate

Dolomites_EN-US3033597177The anterior cingulate cortex is a region of the brain that is activated by sensation, cognition, and emotion. It appears to play an important role in autonomic, affective, and cognitive behavior. Because of its position, the anterior cingulate is anatomically and functionally well positioned to integrate information across the physical, intellectual and emotional domains. Important in the stress reaction, the anterior cingulate region is activated during self-regulation of arousal through its connections with the cholinergic basal forebrain. The whole structure, but especially area 32, produces inhibitory inputs that decrease amygdala responsiveness and are helpful in mitigating the effects of fear and in preventing or at least delaying “amygdala hijacks.”

The normal functioning of the anterior cingulate area leads to a normal response to stressful events, which is a psychophysiological arousal or increased emotionality. The normality of the brain response to traumatic stimuli also serves to inhibit feelings of fear when there is no true threat.  Any chemical or structural failure of activation in this area and/or decreased blood flow in the adjacent subcallosal gyrus can lead to an exaggerated response to stress, resulting in significantly higher emotionality and the inability to properly regulate fear. The latter condition provides the inducing cues in anxiety disorders, i.e. increased and persistent fearfulness that is not appropriate for the context.

What the Anterior Cingulate Does

BrodmanBrainAreasPhysically, stimulation of the anterior cingulate (especially in area 24) induces changes in blood pressure, heart rate, respiratory rate, pupillary dilation, skin conductance, thermoregulation, gastrointestinal motility, and changes in adrenal cortical hormone secretion (ACTH). Cognitively, the anterior cingulate cortex plays a leading role in learning new behaviors, whether as a conditioned response to predictors of painful stimuli, as an instrumental response to avoid such stimuli, or in response to reduced reward. Emotionally, the anterior cingulate (along with other structures in the limbic system) mediates emotional responses including fear, agitation, and euphoria, and verbal expression with affective content, such as sighs, cries, and screams.

Neuroimaging studies with powerful fMRI instruments show electrical activation in the rostral–ventral anterior cingulate cortex when individuals under study are asked to recall sad memories or view faces with sad expressions, when they are told to anticipate an upcoming painful electric shock, and when exposed to scenes or words with emotional content. It should come as no surprise that stress-induced activations in the amygdala and orbitofrontal cortex occur simultaneously with those in the anterior cingulate cortex.

Genes, Stress and the Anterior Cingulate

Genetic studies have conclusively demonstrated that the anterior cingulate cortex is highly sensitive to environmental stressors, either physical, psychological, or behavioral. Anoxia (lack of oxygen), maternal separation, amyloid protein expression, and drug abuse all induce hypometabolism, gliosis, and programmed cell death in the anterior cingulate cortex. After prolonged and continued exposure to stress, nerve cells in the anterior cingulate cortex are damaged and killed by excessive stimulation, a process called excitotoxicity.

When the Anterior Cingulate Malfunctions

Several psychiatric disorders are linked with abnormalities in the function of the anterior cingulate cortex. Significantly elevated neurochemical activity in this region of the brain has been observed in obsessive–compulsive disorder, tic disorder, and depression. A normal range of activity is restored with behavioral and pharmacological treatment of these disorders. Other psychiatric disorders that have been associated with abnormal functioning of the anterior cingulate cortex include attention deficit hyperactivity disorder (ADHD) and schizophrenia.

Stresshacker Not Found. Click To Continue.

Riccio_SH Sometime between midnight and 5 am on Thursday, the computer server that “dishes up” Stresshacker went down. And stayed down. Eventually, during the day, it died. The result was the disappearance of from the Internet. Service was not restored until late on Thursday evening, and not fully (with a new server) until this Friday afternoon, for a total down time of about 12 hours.

First, my apologies to the visitors who tried to access and were met with a screen that proclaimed its disappearance. We have taken the necessary steps and hopefully this type of incident will not happen again.

Second, this was an object lesson on the management of stress and anxiety. My reaction cycled through the stages, from denial (this can’t be happening), to anger (this shouldn’t be), to bargaining (maybe I can get them to fix it fast), to despair (we are down forever!), and finally to acceptance (we can use the down time to research and choose a better solution). The stress process took a couple of hours, while the repairs to the server took six times as long.

The lesson for me: experience the stress fully (I had a darn good reason), let the anxiety ebb and flow, and then get to work to address the real culprit: better Internet service.

Stress Hardware Reviews: The Hippocampus

clip_image001What brain structures rouse us from inactivity and set in motion our defense mechanisms when a stressor is perceived? Predictably, the brain’s older and more primordial area, the so-called animal brain, where the hypothalamus, the amygdala, the hippocampus, the septum area, the basal ganglia and the thalamus are located. These structures, collectively called the limbic system, are interconnected and work together to initiate motor and other functional activities of the brain that mobilize the body. In this post about stress hardware, we discuss the hippocampus.

Virtually any experience perceived by the five senses appears to cause the activation of at least some part of the hippocampus. The hippocampus in turn redistributes these sensory signals to the thalamus, the hypothalamus, and other parts of the limbic system. Thus, the hippocampus acts as an important switching center through which incoming sensory signals are retransmitted and initiate behavioral reactions for different purposes. Its importance has been demonstrated empirically: experimental artificial stimulation of the hippocampus can induce a wide variety of behavioral patterns such as pleasure, rage, passivity, or excessive sexual drive.

The cells of the hippocampus appear to be especially sensitive to the effects of various stressors. Although not directly involved in the stress response, its ventral regions appear to exercise a regulatory influence on the hypothalamic-pituitary-adrenal (HPA) axis activity and are also a primary target for elevated glucocorticoid levels. The glucocorticoid hormones owe their name to their important effects on blood glucose concentration, which is the principal source of energy of the human cell. They also regulate protein and fat consumption, and the utilization of carbohydrates to produce additional quantities of energy. Cortisol is the principal glucocorticoid. Read more