Clinical | Stresshacker

Faith in God Positively Influences Treatment for Individuals with Mental Disorders

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faith-health Belief in God may significantly improve the outcome of those receiving short-term treatment for psychiatric illness, according to a recent study conducted by McLean Hospital investigators. McLean Hospital of Belmont, MA is the largest psychiatric affiliate of Harvard Medical School.

In the study, published in the current issue of Journal of Affective Disorders, David H. Rosmarin, PhD, McLean Hospital clinician and instructor in the Department of Psychiatry at Harvard Medical School, examined individuals at the Behavioral Health Partial Hospital program at McLean in an effort to investigate the relationship between patients’ level of belief in God, expectations for treatment and actual treatment outcomes.

“Our work suggests that people with a moderate to high level of belief in a higher power do significantly better in short-term psychiatric treatment than those without, regardless of their religious affiliation. Belief was associated with not only improved psychological wellbeing, but decreases in depression and intention to self-harm,” explained Rosmarin.

The study looked at 159 patients, recruited over a one-year period. Each participant was asked to gauge their belief in God as well as their expectations for treatment outcome and emotion regulation, each on a five-point scale. Levels of depression, wellbeing, and self-harm were assessed at the beginning and end of their treatment program.

Of the patients sampled, more than 30 percent claimed no specific religious affiliation yet still saw the same benefits in treatment if their belief in a higher power was rated as moderately or very high. Patients with “no” or only “slight” belief in God were twice as likely not to respond to treatment than patients with higher levels of belief.

The study concludes: “… belief in God is associated with improved treatment outcomes in psychiatric care. More centrally, our results suggest that belief in the credibility of psychiatric treatment and increased expectations to gain from treatment might be mechanisms by which belief in God can impact treatment outcomes.”

Rosmarin commented, “Given the prevalence of religious belief in the United States — over 90% of the population — these findings are important in that they highlight the clinical implications of spiritual life. I hope that this work will lead to larger studies and increased funding in order to help as many people as possible.”

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Stress and Memory: An Update

By Dr. Z | Clinical, Stress & Health

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Salvador Dali Persistence of Memory at Stresshacker.com Stress can interfere with the functioning of memory by either augmenting the impact and persistence of the recollection of an event, or by diminishing both. A recent article by Schwabe et al. (2012) summarizes and updates the most recent findings on the effects of stress on memory. Their research concludes that the timing of the exposure to the stressor is crucial in determining whether memory is improved or impaired. Timing may explain why there are stressful situations in which we are unable to retrieve critical information that we have learned prior to the stressor, e.g. an important phone number or address. In contrast, experiencing stress at the same time as we participate in certain embarrassing, shameful, or frightening events can cause a dramatic enhancement of memory formation.

Schwabe and colleagues examine and attempt to integrate two models of how stress may alter memory processes, the “vertical” model (the mechanisms of stress on memory) and the “horizontal” model (the changes in stress effects on memory over time.)

The vertical perspective implicates principally the action of glucocorticoids (GC) and noradrenaline on the basolateral amygdala. In a typical stress reaction, the hypothalamus activates the hypothalamic-pituitary-adrenal (HPA) axis in response to input from several other brain regions and the sympathetic nervous system (SNS). Through the portal blood system, corticotrophin releasing hormone (CRH) and vasopressin flood the pituitary gland, which trigger its secretion of adrenocorticotropic hormone (ACTH). In response to ACTH release from the pituitary, the adrenal glands secrete glucocorticoids (GCs), of which cortisol is the principal component. GCs, which are lipophilic (fat-loving) steroid hormones, enter the brain relatively easily and can exert their excitatory effect in multiple regions throughout the brain. These effects are often mediated through the binding to the two receptors for the hormone: the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptors differ in their affinity for cortisol (with the MR having a much higher affinity) and also in their localization in the brain. In addition, GCs can exert nongenomic effects (occurring rapidly and acutely) by influencing ion channels or neurotransmitter receptors at the membrane level. It is important to note that CRH, vasopressin, and ACTH can, on their own, influence cognition. When released in concurrence with a stressor, they can have an almost instantaneous effect on memory processes.

The horizontal perspective suggests that the memory of an event or cognition is enhanced when new information is acquired during the stressful situation, whereas the memory process is impaired for information that was acquired prior to or after the stressful situation. In these situations, the flood of GCs acutely enhances memory consolidation of emotional arousing material, while significantly impairing memory retrieval. At the moment of greatest stress, the memory of a significantly stressful event is instantaneously etched into the memory banks in vivid and abundant detail. The recollection of a sometimes important and well-known piece of information is inhibited. It is as if the whole of our attention is absorbed, or mobilized, toward the assessment of the threat presented by the stressor and in the formulation of a reaction to it. The excitatory hormones cursing through the blood system rapidly arouse the nervous, cardio-circulatory, respiratory, and endocrine system. There is no time or resource available for other activities that are not related to the defense of the organism against the perceived (or real) threat of the stressor. Included in these “secondary” activities that are postponed as non-critical is memory retrieval of old information.

Other important findings highlighted in this article are the effects of stress on the striatum, a brain structure that was originally associated with motor control but that is now receiving increased attention as one of the loci of mnemonic function. Secondly, memory is affected by stress not only in terms of its quantity, but also its quality. Lastly, the authors cite important research conducted in the last decade which points to the effects of maternal stress during pregnancy or early childhood stress as harbingers of an individual’s impaired performance as an adult in high-stress environments.

The article concludes with several important questions, which provide an indication of the limits of current research in explaining important aspects of memory formation. For example, it remains difficult to understand how the same neurochemicals can exert opposite effects on the same brain structures, or how individuals in similar situations exhibit such differing recollections of the same event, and other similarly unexplored mysteries. These limitations do not detract from the thoroughness and relevance of this article.

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Sympathetic Muscle Tension and Stress

By Dr. Z | Clinical, Stress & Health

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One of the well-known phenomena that accompany the stress response is the spontaneous and uncontrollable action of the sympathetic nervous system on the musculoskeletal structures of the body. Stress, muscular tension and pain often go hand in hand.

The Alarm or Stress Response of the Sympathetic Nervous System

When the sympathetic nervous system is suddenly stimulated by a stressor, there is an almost immediate increase in the body’s ability to carry out unusually vigorous muscle activity, even in individuals who would ordinarily not be capable of it.This almost prodigious increase in strength is facilitated by a cascade of physiological changes that is precipitated by stressful situations.

These changes, which take place in a matter of mere seconds, include:

Increased arterial blood pressure.
Increased blood flow to the muscles along with a corresponding decrease in blood supply to the gastrointestinal tract and the kidneys, which are not needed in mounting the body’s rapid response to the threat.
Increased rates of cellular metabolism, which speed up the body’s rate of functioning.
Increased blood glucose concentration, which provides increased levels of energy.
Increased glycolysis in the liver and in the muscle, also a factor in energy supply.
Increased muscle tension and preparedness to work, which increase tone and strength.
Increased mental activity, which provides acuity, alertness and greater focus on the threat.
Increased rate of blood coagulation, which protects the body from significant blood loss if it should sustain minor cuts and puncture.

The combined effects of the mobilization of virtually all principal organs is what enables the body to perform significantly more strenuous physical activity than it is ordinarily possible. Stress of any kind, physical, emotional or mental, excites the sympathetic system, whose purpose is to provide above-normal activation of the body’s resources. Because of this stimulation, the stress response is often referred to as the sympathetic stress response.

Emotional vs. Physical Stress

The sympathetic system is activated during physical danger, but it is also and more frequently activated by many real or perceived emotional stressors. Guyton-Hall cite the example of anger or rage,

…which is elicited to a great extent by stimulating the hypothalamus, signals are transmitted downward through the reticular formation of the brain stem and into the spinal cord to cause massive sympathetic discharge; most aforementioned sympathetic events ensue immediately. This is called the sympathetic alarm reaction. It is also called the fight or flight reaction because an animal in this state decides almost instantly whether to stand and fight or to run. In either event, the sympathetic alarm reaction makes the animal’s subsequent activities vigorous.
–Textbook of medical physiology by Arthur C. Guyton & John E. Hall, 11th ed.

Chronic Stress

The same exact response can be elicited even daily in individuals exposed to multiple or repeating stressors, such as a negative environment, a dysfunctional relationship, poor working conditions, or difficult socio-economic challenges. In this case, the muscle tension and sympathetic stimulation can be so great and so frequent that the body cannot return to a normal state of relaxation, in which case a chronic stress condition can ensue.

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When Stress Hits You On the Nose

By Dr. Z | Clinical, Stress & Health

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Stress-induced upper respiratory symptoms are not unusual. Stress has a powerful effect on the immune system, as the circulation of high levels of the excitatory hormones that accompany stress undermines its defense mechanisms, often producing symptoms such as those of the common cold.

How Does It Work?

Stress suppresses the activity of the immune system, principally due to the effects of the stress hormone cortisol. When under the impact of a significant stressor, the immune system is “flooded” by cortisol and other hormones and its functioning is, at least temporarily, greatly reduced. Thus, pathogens, such as those producing the common cold, have a relatively easier time entering and proliferating in the upper respiratory system.

This is the most prevalent theory of why people get sick while under stress. It does not affect everyone in the same way, however. For some people, it is not until the stressor is removed that adverse symptoms begin to manifest. In this case, it is almost as if the relaxation produced by the removal of the stressor had the effect of making the individual more vulnerable.

What Can Be Done?

A doctor once was asked how long it would take to cure a cold. His answer was, “Oh, about seven days if you take this prescription, or about a week if you decide not to take anything.” Beside the joke, there is truth in the fact that there is no cure for the common cold, either stress-induced or otherwise. It will generally resolve itself, with or without medication, in about a week or so.

Something can be done however to reduce the effects of stress on the immune system. Some people find help in ingesting large quantities of vitamin C at the onset of their respiratory symptoms. Others find that remedies such as hot baths, hot drinks with honey, breathing exercises, yoga or meditation all have beneficial effects on the effects of stress, and thereby, on the immune system.

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“Rich” Nutrition Linked to Poor Mental Health

By Dr. Z | Clinical, Stress & Health

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killer-fast-food Psychological stress is known to increase the production of pro-inflammatory cytokines. The deriving inflammation is accompanied by an accumulation of highly reactive oxygen species, also known as oxidative stress, which is a contributing factor in the development of severe depression. A diet rich in antioxidants, vitamins, minerals and fiber is associated with reduced systemic inflammation. Conversely, diets that are low in essential nutrients, such as magnesium and sugar- and fat-rich western diets are associated with increased systemic inflammation.

A new study of 3040 Australian adolescents 11 to 18 years of age collected information on diet and mental health by self-report and anthropometric data by trained researchers. Improvements in diet quality were mirrored by improvements in mental health over the follow-up period, while deteriorating diet quality was associated with poorer psychological functioning. Researchers concluded that the quality of one’s nutrition is associated with adolescent mental health both cross-sectionally and prospectively. Moreover, improvements in diet quality were mirrored by improvements in mental health, while reductions in diet quality were associated with declining psychological functioning over the follow-up period.

There are many ways in which an insufficiency of healthy foods and/or an excessive intake of unhealthy and processed foods may increase the risk for mental health problems in adolescents. Fruits and vegetables, as well as other components of a healthy diet such as whole grains, fish, lean red meats and olive oils, are rich in important nutrients such as folate, magnesium, b-group vitamins, selenium, zinc, mono- and polyunsaturated fatty acids, polyphenols and fiber. Many of these nutrients have already been reported as of importance in depressive illnesses, however the critical importance of these food components as modulators of reactive oxygen species (inflammation) and immune system functioning, both pathophysiological substrates of depressive illness is increasingly appreciated.

stressed-desserts A new meta-analysis, reporting on data collected at many time points and thus more reliable, has reported large generational increases in self-reported mental health problems among American high school and college students between the 1930s and 2007. Paralleling this increase in the rates of psychological illness among young people are data indicating a reduction in the quality of adolescents’ diets over recent decades. A report based on trends in adolescent food consumption in the US identified a reduction in the consumption of raw fruits, high-nutrient vegetables and dairy foods, which are important sources of fiber and essential nutrients, between 1965 and 1996, with an associated increase in the consumption of fast food, snacks and sweetened beverages.

Concurrently, population surveys demonstrate a substantial increase in overweight and obesity among children and adolescents over recent decades. Obesity does not necessarily indicate nutritional deficiency: paradoxically, high-energy foods typically have poor nutrient content.

Fast Food, Depression and Anxiety

Another study of 5731 men and women 46 to 49 and 70 to 74 years of age found that those with better quality diets were less likely to be depressed, whereas a higher intake of processed and unhealthy foods was associated with increased anxiety.

USA-Obesity-Rate A third study examined the extent to which the high-prevalence mental disorders are related to habitual diet in 1,046 women 20–93 years of age. Results showed that a “traditional” dietary pattern characterized by vegetables, fruit, meat, fish, and whole grains was associated with lower odds for major depression or log-term depression (dysthymia) and anxiety disorders. A western diet of processed or fried foods, refined grains, sugary products, and beer was associated with a higher prevalence of mental disorders. These results demonstrate an association between habitual diet quality and a higher prevalence of mental disorders.

In a fourth study (1999–2010) of 12,059 Spanish university graduates discovered a detrimental relationship between a diet rich in trans unsaturated fatty acids (TFA) and depression risk, whereas weak inverse associations were found for monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA) and olive oil. These findings suggest that cardiovascular disease and depression may share some common nutritional determinants related to fat intake.

Most notably, results of a 2010 randomized placebo controlled trial showed that fish oil supplements prevented conversion from a subthreshold psychotic state to full-blown schizophrenia. Another recent randomized controlled trial study suggested that omega-3 supplements may help reduce anxiety.

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Lower DHA Intake Linked to Higher Suicidality

By Dr. Z | Clinical, Stress & Health

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ChileVolcanoEruption_EN-US1005377464 Low levels of docosahexaenoic acid (DHA), the major omega-3 fatty acid concentrated in the brain, may increase suicide risk. A retrospective case-control study published in the most recent issue of the Journal of Clinical Psychiatry of 1600 United States military personnel, including 800 who had committed suicide and 800 healthy counterparts, showed that all participants had low omega-3 levels. However, the suicide risk was 62% greatest in those with the lowest levels of DHA.

Our findings add to an extensive body of research that points to a fundamental role for DHA and other omega-3 fatty acids in protecting against mental health problems and suicide risks. — Joseph R. Hibbeln, MD, acting chief, Section on Nutritional Neurosciences at the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland

DHA is found in naturally in fish and nuts and is also available in fish oil supplements. Fish oil supplements can help lower inflammation by decreasing the synthesis of proinflammatory molecules and have been proven beneficial in treating inflammatory diseases, such as rheumatoid arthritis and Crohn’s disease. Although fish oil has been shown to be less effective in treating other stress-related illnesses such as ulcerative colitis and asthma, some patients do benefit from its intake.

The omega-3 fatty acids EPA and DHA contained in fish oil are effective in treating both cardiovascular disease and depression, often in combination with other specific medications. Higher levels of EPA and DHA are also associated with increased stress resilience.

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Cellphone Use & Cancer: Risks and Opinions

By Dr. Z | Clinical, Stress & Health

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cellphone_brain On May 31, 2011 the World Health Organization (WHO) announced their classification of radiofrequency (RF) electromagnetic fields emitted from cell phones, used globally by more than 4.6 billion people, as "possibly carcinogenic to humans.” Given the serious health risk that this implies, WHO has pledged to conduct a formal risk assessment of all studied health outcomes from radiofrequency fields exposure by 2012.

The Current Evidence of Cancer Risk

A study conducted in Denmark from 1982 to 1995 (with a follow-up in 2002) analyzed cancer rates among 420,095 cell phone users and found no increased risk for brain tumors, salivary gland tumors, eye tumors, or leukemia.
A number of earlier and smaller case–control studies as well as more than 40 experimental studies also found no direct association between cell phone use and cancer.
The INTERPHONE study, the largest of its kind to date, examined 2,708 glioma and 2,409
meningioma cases in 13 countries using a common protocol. This study found that using a cell phone appeared to slightly lower the risk of developing a glioma, compared with never using one. But, when the highest 10% of cell phone users in terms of call time were analyzed, this subgroup had a 40% increased risk for glioma, compared with those who had never used a cell phone. Thus, according to Interphone, there is a higher risk for tumors occurring on the same side of the brain as cell phone exposure, and especially for tumors located in the temporal lobe, where RF exposure is highest.
A meeting of 31 scientists organized by the International Agency for Research on Cancer (IARC) in Lyon, France, whose results have been just published in the latest issue of the medical journal The Lancet, considered the potential carcinogenic hazards from exposure to RF electromagnetic fields emitted by cell phones. The IARC group concluded that fields emitted by cell phones should be considered as "possibly carcinogenic" to humans.
A pooled analysis of Swedish studies examined the association between cell and cordless phone use and glioma, acoustic neuroma, and meningioma in 1,251 (85%) cases and 2,438 (84%) controls. For people who had used a cell phone for more than 1 year, the risk for brain tumors was 1.3 times higher (30%) than in people who had never used a cell phone. This risk increased with time since first use and with total call time. After more than 2000 hours of use, the risk was 3.2 times as high. Similar results were observed among cordless phone users.

In addition to the comprehensive review planned by WHO, the Cohort Study on Mobile Communications (COSMOS) is attempting to do a similarly all-inclusive study. It will become the largest study ever conducted and examine the effects of cell phone use on long-term health. COSMOS plans to track at least 250,000 people in 5 European countries for up to 30 years and it will not rely on users’ self-report, but will follow cell phone use in real time.

The Opinions On Cell Phone Use and Cancer Risk

aaKandinsky_YellowRedBlue Dr. Jonathan Samet, Chair of the IARC working group and the Flora L. Thornton Chair of the Department of Preventive Medicine at the Keck School of Medicine, University of Southern California, Los Angeles, , explains that "possibly carcinogenic" means is that cell phone use is not completely safe, although it needs to be more clearly defined through better investigation. If users want to do something about the risk, says Dr. Samet, “there are easy steps to take to lower exposure, such as using hands-free devices and reducing use of the phone."

Other researchers point out that exposure to RF fields is not limited to cell phones but can be caused by other personal devices. Moreover, the specific absorption rate varies from one phone model to another and it can be affected by many factors, including the design, the position of the phone and its antenna in relation to the head, how the phone is held, the anatomy of the head, and the quality of the link between the base station and the phone.

Children are more at risk than adults, since the average RF energy deposition in a child’s brain is generally at least twice as high as in adults. In the most sensitive area of the head, the bone marrow of the skull, exposure in children can be up to 10 times as high as in adults.

Researchers also point out that the INTERPHONE study and the Swedish pooled analysis may not be entirely accurate due to the possibility of "recall error and selection for participation," although the results of these studies cannot be dismissed as reflecting bias alone, since a cause-effect relationship between cell phone-caused exposure to RF fields and brain cancer remains a distinct possibility.

More, Better Research Needed

Where does this leave cell phone users, all 4.6 billion of them? More studies are certainly needed and, perhaps most importantly, the studies need to be better designed. Studies which rely on interviews and on the participants ability to recall the details of their phone use do not produce the most reliable results. Prospective studies that track phone use and health records in real time, that are large enough to include significant segments of the population will produce far more accurate results. They are being planned and, in the case of the COSMOS study, they are underway. Until then, Bluetooth earpieces would seem the way to go.

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How Good and Bad Stress Are the Same

By Dr. Z | Clinical

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MountRotui_EN-US1706638791 Eustress (or good stress) and bad stress (acute or chronic) cause the exact same reaction in the human body. Even during voluntary “stressful” activities such as sport or exercise or when we receive unexpected good news, the brain stem, the oldest and more primordial part of the human brain, immediately mobilizes the body’s resources. The brain stem does not know, and one might say does not care, what triggers the sudden demand for additional physical activity. All the brain stem knows, prior to any higher brain intervention such as a decision to be afraid of something, or a decision to exercise, is that more blood is needed immediately to fulfill physical demands that may already be occurring (in the case of exercise or a real and impending threat) or that may be presumed to occur (in the case of perceived danger in a situation).

When the motor areas of the brain and the limbic system become activated by a positive but sudden event, most of the reticular activating system of the brain stem is also mobilized. This activation includes greatly increased stimulation of the vasoconstrictor and cardioacceleratory areas of the vasomotor center of the brain stem. Thus, the increase in arterial pressure permits to keep pace with an expected increase in muscle activity. A similar rise in pressure occurs during negatively stressful situations. The need to prepare to meet the danger posed by the stressor mobilizes the reticular activating system and the vasomotor center of the brain stem.

During dangerous situations (real or perceived), arterial pressure rises to as high as twice its normal value within a few seconds. This dramatic increase can immediately supply blood to any or all muscles of the body needed to respond. This translates into an enormously increased ability to fight against or to flee from the cause of danger. It is indeed a significant survival factor that no conscious decision is needed when this split-second mobilization is required.

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3 Good Ways of Responding To a Panic Attack

By Dr. Z | Clinical, Stress & Health

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OBriensTower_EN-US194301618 A panic attack ambushes the mind, the body, and the soul. Its targets are self-esteem, a balanced self-assessment and the ability to analyze situations and expected outcomes. When panic strikes, the present becomes a bleak landscape of dangers and the future includes a (seemingly) real possibility of annihilation. In the presence of a real (or perceived) significant stressor, one’s abilities to respond to the challenging situation becomes severely impaired. For the span of the panic attack, chest pains, shortness of breath, shaking, sweating, and even nausea and vomiting can give the sensations of impeding death. Can something be done to prepare for a panic attack with any degree of success?

One: Know Thyself

A first important tool is the ability to anticipate one’s own reactions, by getting to know them well enough so that they do not become stressors in themselves. Knowing the likelihood (and thus anticipating the possibility) of the physical sensations that go with feelings of panic (chest constriction, shortness of breath, increased heart rate, and sweating) may help avoid the distress that these symptoms can cause. The very fact of knowing that these physiological reactions will take place, and allowing them to happen as a natural and understandable reaction to a threat to our well-being, can be beneficial.

Two: Know About Panic

Panic attacks are about as close to feeling imminent death as one can get, as anyone who has experienced them in all their severity will attest. A panic attack occurs without anyone else’s intervention (usually no one else is present). It can be extremely frightening even when no real physical danger exists (it can strike a person comfortably seated in his or her favorite recliner). A panic attack, by definition, occurs without any clinical danger of death and cannot by itself cause death or serious injury. A the most, when it reaches a certain level, a panic attack may trigger a loss of consciousness through hyperventilation (prolonged shallow breathing). This usually resolves the physical symptoms by momentarily taking the brain out of the picture, whereby the body can returns to homeostasis. When the person comes to, usually the panic attack is gone just as suddenly as it came. Exhaustion is not infrequent at this stage, as a panic attack can be a real workout for the heart and muscles.

Three: Manage Your Response

BearAttack A useful tool in preventing the recurrence of panic attack is stress management. Allowing the body to react, in concert with the mind, to a situation that may objectively warrant fear, sadness or worry is not only strategically sound, it is also physiologically healthier. Just as courage is not the absence of fear but simply good fear management, allowing a naturally-occurring biopsychic reaction to a stressor is simply good stress management.

Thus, the key to successful panic attack management is not in denying or attempting to prevent the stress reaction, but in what to do next (our chosen response). After the initial physical reaction ebbs and subsides and the heart rate naturally returns to near-normal levels, the real stress management response has a chance to begin. This response should first and foremost consist of addressing the stressor that is causing the panic attack to occur.

3 Good Ways of Addressing Serious Stressors

Three options usually exists in addressing significant stressors:

Eliminating the stressor that caused the panic attack to occur.
Removing oneself from the stressful situation, if option 1 is not available.
Reducing the impact of the stressor through relaxation techniques or good coping mechanisms, when options 1 and 2 are not available.

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Stress Hardware Review: The HPA

By Dr. Z | Clinical, Stress & Health

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ScenicSkyway_EN-US2786891862 In 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.

PituitaryGland The 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.

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Optogenetics Discovers Brain Anxiety Circuit

By Dr. Z | Clinical, Stress & Health

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AmygdCingGyrus The state of heightened apprehension and high arousal in the absence of immediate threat—commonly labeled as acute stress or anxiety—can be a severely debilitating condition. Over 28% of the population suffers from anxiety disorders that contribute to the development of major depressive disorder and substance abuse. Of all the structures of the limbic system, the seat of emotion processing, the amygdala plays a key role in anxiety, although by what exact mechanism still remains unclear. Newly published research carried out by a group of neuroscientists at Stanford University using the novel technique of optogenetics with two-photon microscopy has permitted a much closer exploration of the neural circuits underlying anxiety than ever before. The optogenetics approach facilitates the identification not only of cell types but also the specific connections between cells. The researchers noticed that timed optogenetic stimulation of the basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA) produced a significant, acute, and reversible anxiety-reducing effect. Conversely, selective optogenetic inhibition of the same projection resulted in increased anxiety-related behaviors. These results indicate that specific BLA–CeA projections are the critical circuit elements for acute anxiety control in the brain. The results were published in the March 17 issue of the scientific journal Nature.

A Closer Look at the Amygdala’s BLA and CeA Regions

BasolateralAmygdala The amygdalae (amygdaloid nucleus) are two identical almond-shaped brain structures located in each temporal lobe. Each amygdala receives input from the olfactory system, as well as from visceral structures. The amygdala in humans has been confirmed by functional MRI imaging to be the area of the brain that is best correlated with emotional reactions and plays a key role in the brain’s integration of emotional meaning with perception and experience. The emotional aspect of the response of the individual is passed on to the frontal cortex, where “decisions” are made regarding possible responses. In this way, the response of the individual can take into account the emotional aspect of the situation.

Additionally, the amygdala coordinates the actions of the autonomic and endocrine systems and prompts release of adrenaline and other excitatory hormones into the bloodstream. The amygdala is involved in producing and responding to nonverbal signs of anger, avoidance, defensiveness, and fear. The amygdala has been implicated in emotional dysregulation, aggressive behavior, and psychiatric illnesses such as depression. It has also been shown to play an important role in the formation of emotional memory and in temporal lobe epilepsy.

The basolateral amygdala, one of the two structures studied in the recent Stanford research, receives extensive projections from areas of the brain cortex that are specialized for recognizing objects such as faces in central vision. Extensive intrinsic connections within the amygdala
promote further coordination of sensory information.

Biological effects initiated by amygdala include increases or decreases in arterial pressure and heart rate, gastrointestinal motility and secretion, evacuation, pupillary dilation, piloerection, and secretion of various anterior pituitary hormones, especially the gonadotropins and
adrenocorticotropic hormone, which are key agents in the stress reaction. Interestingly, amygdala stimulation can also cause several types of involuntary movement, such as raising the head or bending the body, circling movements, occasionally rhythmical movements, and movements
associated with taste and eating, such as licking, chewing, and swallowing.

LimbicSystemGeography The findings also show the involvement of the amygdala’s CeA region in mediating threat-related anxiety and acute fear-related behavioral and hormonal responses. Earlier studies had shown that stimulation of this same area reduces snake fear and pituitary-adrenal activity and that CeA lesions resulted in decreased expression of threat-induced freezing. Additionally, the CeA region of the amygdala was reported as being significantly involved in the consolidation of contextual fear memory, i.e., what permits us to remember so vividly and persistently objects or situations that have caused fear in us in the past.

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Ultimate Stressors: Public Drama, Private Pain

By Dr. Z | Clinical, Stress & Health

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charlie-sheen Recently televised interviews with Mr. Charlie Sheen appear to have focused attention on the symptoms and manifestations of the manic phase of bipolar disorder. A public display of inflated self-esteem or grandiosity, profuse talkativeness, increase in goal-directed activity, psychomotor agitation, and the excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish investments) are the textbook criteria for a manic episode. More privately, the individual in the grip of mania also experiences a decreased need for sleep, flight of ideas or racing thoughts, and distractibility. When this disturbance is sufficiently severe, it can cause marked or total impairment in occupational functioning, usual social activities and relationships with others and may necessitate hospitalization to prevent self-harm or harm to others. Episodes of mania, whose symptoms are the opposite of those denoting depression, are rarely seen alone. Usually, the manic state is preceded and followed by depressive periods in an alternating fashion, with each state lasting from many months to a few weeks, the latter being described as ‘‘rapid cycling.’’

This constellation of symptoms was known, until a few years ago, as manic-depressive disorder. Nowadays, it goes by the somewhat more cryptic label of bipolar disorder. The neurochemical basis of bipolar disorder is not exactly known. One of the most valid hypotheses regarding the neurochemical mechanisms of bipolar disorder is the synergy between two neurotransmitters that determine mood states, whereby a lower than normal release of norepinephrine produces a disordered mood (significantly higher or lower than the normal range), while the levels of serotonin determine the direction the symptoms will take, i.e. downward toward depression or upward toward mania.

What Bipolar Disorder Feels Like

The subjective experience of these intense mood swings ranges from abject despair and hopelessness to not entirely distressing and almost pleasurable. Depression produces a pervasive
and relentless sense of gloom, inadequacy, rumination, guilt, and worthlessness. No logic, willful effort or remembrance of wellness seems capable of dispelling these cognitive and emotional experiences, often for prolonged periods.

Mania reverses and accelerates upward from the disappearance of depression, through a state of well-being that can be considered a normal mood state. Normality soon becomes exuberance, enters into a state of unexplained euphoria, and finally culminates into a chaotic state of racing, incomprehensible, disconnected thoughts, and bizarre behaviors. Given a choice, the individuals so affected report that they much prefer the state of mania, in which they experience a release from inhibitions, a hedonistic focus, and a pursuit of pleasure and gratification that can be nearly devoid of accountability or restraint. Self-medication with alcohol and illegal drugs is often present in the manic phase, which sets up a circular relationship that exacerbates its symptoms and impedes treatment and recovery.

An individual in a state of mania can be frightening, annoying, or amusing to the casual observer. It is perhaps easy to overlook the nature of the behavior, especially when there is an assumption of intent. In most cases, however, the individual has virtually no control over thoughts, words and behaviors and little if any insight into their bizarre, provocative, and sometimes dangerous presentation. The loss of reality testing, judgment and moral restraint of bipolar disorder is sure to cause psychological pain to the people who experience it and to the people who love them. Mr. Charlie Sheen has been variously portrayed as victim and perpetrator, and variously diagnosed by experts and entertainment reporters.

Bipolar Disorder: A Brief History

The first connection between a manic state and depression as belonging to the same neurochemical disorder was established in 1686 by the French physician Theophile Bonet, who observed individuals who appeared to cycle between high and low moods, and described their presentation as ‘‘manico-melancolicus.’’ In the middle of the 19th century, two other French researchers, Falret and Baillarger, who had independently observed the same cycling of moods in their patients, arrived at the same conclusion that the symptoms must be two different presentations of the same illness. Falret described the disorder as ‘‘circular insanity’’ and hypothesized a hereditary component to the disorder. In the late 1800s to early 1900s, German psychiatrist Emil Kraepelin elaborated the description and classification for manic–depressive illness that is considered the standard presentation that we see today.

It was John F. J. Cade, a doctor in the Mental Hygiene Department of Victoria, Australia, who introduced and promoted the belief that manic–depression was a biological disorder of the brain. On the basis of his research on neurochemistry, Cade administered a lithium salt preparation to several highly agitated manic patients and observed a remarkable reduction in symptoms, with a near return to a normal mood state. Lithium is currently the standard of care for the pharmacological treatment of bipolar disorder, and still the most effective in the management of its symptoms.

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Worst Stress Relievers: Pain Medication

By Dr. Z | Clinical, Stress & Health

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Who is to say for sure how much pain I have right now, I had yesterday morning, or will have this afternoon? Only I can know for sure the pain I am feeling—and I can lie, to myself and to others. Herein lies the greatest challenge of addiction to pain medication. There is no objective measuring tool for pain. The best we can do is to ask the person to rate his or her own pain on a scale of 1 to 10, with all the accuracy that can be expected from such a subjective assessment, which isn’t very much because pain can always feel more intense than it actually is, physically or sometimes just psychologically.

The sad result of the greater availability of pain medication, its greater potency, the beneficial effects felt by the individual by taking what amounts to a legal hit of morphine is an ever increasing number of people who are dying from abusing or misusing pain medication. Among some groups, deaths from prescription drug overdoses are more than ten times higher than they were in the late 1960s. These are the results of an age-period-cohort analysis using data from the US Vital Statistics and the US Census, available online.

In the absence of significant pain, prescription painkillers are ingested because of their very powerful relaxing effects on the central nervous system and for the sensations of well-being that characterize their action. The presence of hydrocodone, which is the equivalent of synthetic opium, in these drugs makes them highly addictive. The first signs of a painkiller overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in the upper stomach, dark urine, and yellowing of the skin or the whites of the eyes. Overdose symptoms may also include extreme drowsiness, pinpoint pupils, cold and clammy skin, muscle weakness, fainting, weak pulse, slow heart rate, coma, blue lips, shallow breathing, or no breathing.

The rapid increase in mortality due to accidental poisoning that has been observed since 2000 is almost tenfold for whites and threefold for blacks over the study period. This appears to result at least in part from the coming of age of baby boomers who, as they age, are becoming addicted to prescription medications, most especially pain killers. The majority of prescription drug abuse involves painkillers, according to the Drug Enforcement Administration. In the US, Vicodin (containing acetaminophen and hydrocodone) is the most commonly abused prescription drug.

The greatest proportion of overdoses appears to occur in people in their 40s and 50s. While in 1968 about one per 100,000 white women in their early 50s died from accidental poisoning, the number has risen to 15 per 100,000 in 2007. Among black women of the same age, accidental poisoning deaths increased from about two per 100,000 to almost 17 per 100,000.

What’s the fix for this nationwide epidemic? In the absence of an objective pain measure, it is hard to imagine how anyone can take exception to the screams of pain that can come from someone who is in the process of becoming addicted to pain medication, or already is. Many doctors have taken the no-hassle course of prescribing, rather than questioning the veracity of the patient’s pain. Many other medical practitioners, such as dentists and surgeons, have taken to dispensing large quantities of “samples” to patients who have had even the simplest procedure, “just in case you feel any pain.” Of course, the patient takes the stuff, the pain (if any) goes away, and the powerful effects of the drug go to work by inducing a high that feels incredibly good. At this point, and in many sad cases, only a few short steps separate the patient from the addict.

More recently, the DEA has cracked down on pharmacies and doctors, with the intent of reducing the supply of these medications. More needs to be done to stop the flow, but also and most especially to educate the public on the potential addictive nature of these substances. They do work extremely well against pain, but at what cost?

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Marijuana Linked to Earlier Onset of Psychosis

By Dr. Z | Clinical, Stress & Health

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Manifesti_LotteriaTripoli_194_m Marijuana (cannabis), thanks to the powerful depressing action of its active ingredient tetrahydrocannabinol (THC), is one of the oldest and most widely used means of self-medication against acute and chronic stress. THC users report experiencing a pleasurable state of relaxation, with heightened sensory experiences of taste, sound and color. In addition to its psychological effects, THC produces alterations in motor behavior, perception, cognition, memory, learning, endocrine function, food intake, and regulation of body temperature. The common perception is that, of all illegal drugs, marijuana may be the safest and least addictive—despite significant evidence that it causes side effects of fatigue, paranoia, memory problems, depersonalization, mood alterations, urinary retention, constipation, decreased motor coordination, lethargy, slurred speech, and dizziness, in addition to increased tolerance and addiction.

Impaired health including lung damage, behavioral changes, and reproductive, cardiovascular and immunological effects have been associated with regular marijuana use. Regular and chronic marijuana smokers may have many of the same respiratory problems that tobacco smokers have (daily cough and phlegm, symptoms of chronic bronchitis), as the amount of tar inhaled and the level of carbon monoxide absorbed by marijuana smokers is 3 to 5 times greater than among tobacco smokers. Smoking marijuana while shooting up cocaine has the potential to cause severe increases in heart rate and blood pressure. – NHTSA Fact Sheet

New research suggests that marijuana use may play a direct causal role in the development of psychotic disorders, including schizophrenia. An extensive meta-analysis of more than 443 studies comparing the age at onset of schizophrenia in individuals who used marijuana with the age at onset of schizophrenia in non–users yielded most sobering results.

Investigators at Prince Wales Hospital and the School of Psychiatry at the University of New South Wales in Sydney, Australia, found that the mean age at illness onset was more than 2.7 years earlier for cannabis users compared with nonusers. The age of onset did not significantly differ between alcohol users and nonusers. These results were published in the February 2011 issue of the Archives of General Psychiatry.

The results support the hypothesis that cannabis use plays a causal role in the development of psychosis… (and) suggest the need for renewed warnings about the potentially harmful effects of cannabis. – Matthew Large

In presenting the findings, lead study author Matthew Large, MBBS, Department of Mental Health Services concluded that the meta-analysis provides strong evidence for a relationship between marijuana use and earlier onset of psychotic illness and of a direct causal role in the development of psychosis in some more vulnerable individuals.

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Stress and the Female Brain Advantage

By Dr. Z | At Home, At Work, Clinical

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drlouannbrizendine In 1994, Louann Brizendine, a neuropsychiatrist at the University of California, established the Women’s Mood and Hormone Clinic in San Francisco—one of very few such institutions in the world—and focused her attention on the etiology and functioning of the female nervous system.

In 2007, she published The Female Brain as the culmination of her 20 years of research and a compendium of the latest findings from a range of disciplines. It is a fascinating and, in some ways, startling revelation of the most noteworthy particularities that characterize the human female brain.

Size Does Matter… and So Does Density

Women and men have very nearly the same number of brain cells, even though the female brain is about 9% smaller than men’s. This fact had been known for some time and had been, more or less jokingly, interpreted as meaning that women were not as smart. Dr. Brizendine reveals a much simpler explanation: women’s brain cells are more tightly packed into the skull.

To further dispel any notion of masculine brain superiority, she says, women have 11% more language and hearing neurons than men and a larger hippocampus, the area of the brain that is most closely associated with memory. Much more developed in female brains than male’s is also the circuitry for observing emotion on other people’s faces. Dr. Brizendine concludes that, when it comes to speech, emotional intelligence, and the ability to store richer and more detailed memories, women appear to possess a richer brain endowment and thus a natural advantage.

The amygdala in males, on the other hand, has far more processors than in females, which could explain men’s greater intensity in perceiving danger and their higher proneness to aggression. The male body is much quicker to mobilize to anger and take violent action in reaction to an immediate physical danger.

Are women not as capable of reacting to danger? Dr. Brizendine says that a woman’s brain is as capable to perceive danger or deal with life-threatening situations, but that it mobilizes the body’s resources in quite a different way. The female brain appears to be wired to perceive greater stress over the same event than a man’s. This greater arousal and more forceful stress reaction appears to be a natural way to ensure adequate protection against all possible risks to her children or family unit. Brizendine suggests that this ancestral reason may account for the way a modern woman may view unpaid bills as catastrophic and naturally perceive them more intensely threating to the family’s very survival.

[amtap book:isbn=0767920104]

MRI scans have pushed knowledge much higher by allowing the observation of the workings of the brain in real time. The brain lights up in different places depending on whether it is stimulated by love, looking at faces, solving a problem, speaking, or experiencing anxiety. What lights up, where and when, is different between men’s and women’s brains. Women use different parts of the brain and different circuits to accomplish the same tasks, including solving problems, processing language, and generally experiencing the world.

This is a fascinating book for the scientist and the novice alike, well worth reading. It is the Stresshacker Recommended selection for this month.

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