“This is the first time cortisol reactivity has been identified as a mediator between depressed mood and obesity in girls,” said Elizabeth J. Susman, the Jean Phillips Shibley professor of biobehavioral health at Penn State. “We really haven’t seen this connection in kids before, but it tells us that there are biological risk factors that are similar for obesity and depression.”

Cortisol, a hormone, regulates various metabolic functions in the body and is released as a reaction to stress. Researchers have long known that depression and cortisol are related to obesity, but they had not figured out the exact biological mechanism.

Although it is not clear why high cortisol reactions translate into obesity only for girls, scientists believe it may be due to physiological and behavioral differences — estrogen release and stress eating in girls — in the way the two genders cope with anxiety.

“The implications are to start treating depression early because we know that depression, cortisol and obesity are related in adults,” said Susman.

If depression were to be treated earlier, she noted, it could help reduce the level of cortisol, and thereby help reduce obesity.

“We know stress is a critical factor in many mental and physical health problems,” said Susman. “We are putting together the biology of stress, emotions and a clinical disorder to better understand a major public health problem.”

Susman and her colleagues Lorah D. Dorn, professor of pediatrics, Cincinnati Children’s Hospital Medical Center, and Samantha Dockray, postdoctoral fellow, University College London, used a child behavior checklist to assess 111 boys and girls ages 8 to 13 for symptoms of depression. Next they measured the children’s obesity and the level of cortisol in their saliva before and after various stress tests.

“We had the children tell a story, make up a story, and do a mental arithmetic test,” said Susman. “The children were also told that judges would evaluate the test results with those of other children.”

Statistical analyses of the data suggest that depression is associated with spikes in cortisol levels for boys and girls after the stress tests, but higher cortisol reactions to stress are associated with obesity only in girls. The team reported its findings in a recent issue of the Journal of Adolescent Health.

“In these children, it was mainly the peak in cortisol that was related to obesity,” Susman explained. “It was how they reacted to an immediate stress.”

The National Institutes of Health supported this work.

Source:
Amitabh Avasthi
Penn State

A cluster-headache sufferer can wake up during the night because of the pain. Often, this occurs at the same time each night. The eye on the painful side of the head may be reddened and watery. The individual’s nose may be runny or blocked on the side of the nose where the pain is.

In northern countries cluster headaches tend to occur more frequently during the autumn (fall) and spring. Alcohol or extreme variations in temperature can trigger an episode during a cluster period – generally, the change in temperature refers to a rapid rise in body temperature.

Cluster headache attacks occur cyclically, hence the name. A bout of regular attacks – cluster periods – can last from a few days, weeks, to even months. This is followed by remission periods during which no headaches are felt.

Cluster headaches are not very common – they are said to affect about 1 in every 1,000 people. They affect men more often than women; about 80% of sufferers are men, most of them smokers. Fortunately, they generally have no long-term effects on the sufferer’s physical health. There are drugs, such as sumatriptan, and therapies, such as oxygen therapy, available which can significantly reduce the number and intensities of headaches.

Each cluster can last from 15 minutes up to several hours – the majority of cases do not last more than an hour. Typically, a patient will suffer from one to three clusters each day.

According to Medilexicon’s medical dictionary:

Cluster headache is “possibly due to a hypersensitivity to histamine; characterized by recurrent, severe, unilateral orbitotemporal headaches associated with ipsilateral photophobia, lacrimation, and nasal congestion.”

What are the signs and symptoms of cluster headaches?

A symptom is something the patient feels and reports, while a sign is something other people, including a doctor or a nurse may detect. For example, pain may be a symptom while a rash may be a sign.

Symptoms come on rapidly, generally without any warning, and they may include:

• Intense pain, some describe it as excruciating. The pain is continuous, rather than throbbing. The pain often starts around the eye, and may then radiate to other parts of the head, including the face, and down to the neck and even the shoulders. Many patients feel pain in a temple or cheek.
• The pain remains on one side of the head
• The patient becomes restless.
• The eye on the side of the pain is watery and tearful
• The eye on the side of the pain reddens
• There may be swelling around the eye on the pain side
• Stuffy, blocked, or runny nose on the pain side
• Pallor – skin of the face is pale
• Face is sometimes sweaty
• Pupil size may shrink
• Eyelid on the pain side may droop

Patients often describe their pain as stabbing, sharp, burning and penetrating; as if a hot poker had been plunged into one of their eyes. The individual will usually pace around during the episodes of pain, unable to stay still for long. When they sit many may rock back and forth in an attempt to sooth the discomfort (sometimes this helps).

While migraine sufferers prefer to lie down during an attack, people with a cluster headaches say that lying down worsens the pain.

Chronology of cluster headaches (time patterns)

A cluster period typically lasts from 1 to 12 weeks. They often start at similar calendar moments – perhaps during springtime or at some time in the fall (autumn).

• Episodic cluster headaches – patients experience a series of searing headaches for about one week. Then nothing for six to twelve months. Then the week repeats itself.
• Chronic cluster headaches – in this case the cluster periods can persist for several months, even for a year or longer. While periods of remission (periods with no pain) are short; perhaps just a month long.

A cluster period may consist of:

• Daily occurrences, with symptoms appearing several times each day.
• Just one attack, lasting from 15 minutes to up to three hours.
• Attacks occur each day at approximately the same time.
• Most attacks occur between 9pm and 9am (source: The Mayo Clinic, USA)

The pain will suddenly go as quickly as it appeared. Sufferers will be pain-free afterwards, and are often worn out.

If you start getting headaches, it is advisable to see your doctor. Usually, headaches do not have an underlying cause (some illness or condition). However, sometimes they do. It is important for the doctor to rule out any possible underlying causes.

What are the risk factors for cluster headaches?

In medicine, a risk factor is a condition, illness, situation or environment which raises the risk of developing a disease or condition. For example, obese people are more likely to develop diabetes type 2 compared to people of normal weight. Therefore, obesity is a risk factor for diabetes type 2.

For cluster headaches, the risk factors include:

• Being male – approximately 8 in every 10 sufferers are male.
• Being an adult – nearly all suffers say their cluster headaches started after they were 20 years old.
• Ethnic ancestry – people of African ancestry are twice as likely to suffer from cluster headaches, compared to Caucasian people.
• Smoking – the majority of male sufferers are smokers.
• Alcohol consumption – a significant proportion of sufferers claim that alcohol is a key trigger during a cluster period (not during remission periods).
• Genetics – if you have a close relative (parent or sibling) who has (had) cluster headaches, your risk of having them yourself is greater.

What are the causes of cluster headaches?

Experts are unsure why cluster headaches occur. Some researcher neurologists have found that during an attack there is a great deal more activity in the hypothalamus – an area of the brain that controls body temperature, hunger, and thirst. It is suggested that perhaps that area of the brain releases chemicals that cause blood vessels to widen, resulting in a greater bloodflow to the brain, and subsequent headaches.

If the hypothalamus does act in this way, nobody knows why. We do know that such things as alcohol or a sudden rise in temperature, or exercising in hot weather may trigger attacks.

The cyclical nature of cluster headaches suggests there it may be linked to our biological clock, which is located in the hypothalamus.

Hormones – researchers have found that many people who suffer from cluster headaches have unusual levels of melatonin and cortisol during their attacks.

Apart from alcohol, cluster headaches are not linked to the consumption of any foods. No association has been found between cluster headaches and mental stress or anxiety. Even with alcohol, it is only a trigger when the sufferer is in the middle of a cluster period.

Experts say there may be a link between cluster headaches and some medications, such as nitroglycerin, which is used for the treatment of heart disease.

What are the treatment options for cluster headaches?

Currently, there is no treatment that can get rid of cluster headaches completely – there is no cure. Modern therapy aims to alleviate some of the symptoms, shorten the periods of headaches, and reduce their frequency.

OTC (over-the-counter, no prescription required) painkillers, such as aspirin or ibuprofen are not effective for cluster headaches; because the pain comes on rapidly and goes away quickly too. By the time the medication has started to work the headache has probably gone. Therefore, many medications and treatments for cluster headaches are either aimed more at prevention, or fast action.

Fast-acting treatments (acute treatments)

• Inhaling 100% oxygen - most patients find that if they breathe in oxygen through a mask at 7 to 10 liters per minute they experience significant relief of symptoms within 15 minutes. The only problem with this therapy is that the patient has to have an oxygen cylinder and regulator close at hand – carrying them around can be cumbersome. There are some small units on the market. In some cases this kind of therapy only postpones symptoms, rather than alleviating them.
• Injectable sumatriptan (limitrex) – this belongs to a class of drugs introduced in the 1990s (Triptans) for the treatment of migraine. It acts as an agonist for 5-hydroxytryptamine (5-HT) receptors. It is also an effective acute (rapid acting) treatment for cluster headaches. This type of drug may also be taken in nasal spray form – zolmitriptan (Zomig) – but only works for some patients. The adult dose is 6mg (injection); patients may take up to two injections in one 24 hour period as long as each one is at least an hour apart.

  Patients with uncontrolled hypertension (high blood pressure) or ischemic heart disease should not take this drug.

• Dihydroergotamine – an effective pain reliever for some sufferers. It can be taken intravenously or through inhalation. If taken intravenously, the patient needs to go have an IV (intravenous) line in a vein, which is done either in a hospital or doctor’s office. Although also effective, the inhaler form is not as fast-acting.
• Octreotide (Sandostatin, Sandostatin LAR) - a synthetic version of somatostatin; a brain hormone. It is injected. This effective treatment for cluster headaches is considered safe for patients with hypertension and/or ischemic heart disease.
• Local anesthetic nasal drops – an example includes lidocaine (Xylocaine). It is very effective for the treatment of cluster headaches.
• Surgery – if patients do not respond adequately to aggressive treatments, or cannot tolerate some medications, surgery may be recommended – even so, surgery is very rare. Surgery can only be performed once, and is only suitable for sufferers who have pain on just one side of the head. Surgical procedures include:
  • Conventional surgery – the surgeon cuts part of the trigeminal nerve, which serves the area behind and around the eye. This is not a procedure of first choice as there are risks to the patient’s eye.
  • Glycerol injection – glycerol is injected into the facial nerves. This effective treatment is safer than other surgical procedures.
• Stimulator (still being tested) – a small device is implanted over the occipital nerve and sends impulses via electrodes. According to researchers from the Mayo Clinic, USA, a significant number of patients experienced reduced chronic headache pain. The device appears to be well tolerated and safe to use. Another study is looking into implanting a stimulator in the hypothalamus. The National Institute for Health and Clinical Excellence (NICE), the UK body that approves drugs and therapies for National Health Service (NHS) use, has not yet assessed either treatment.

Preventive treatment

Most cluster headache sufferers take short and long term medications. When each period of clusters is over, the short term treatments will stop, but the long-term ones may continue. If cluster headache attacks occur frequently or last for over three weeks, preventive treatments are generally needed. This means taking the treatment the moment headaches start, and throughout the period of headaches until they end.

• Short-term drugs – these are taken until one of the long-term medications start working. Examples include:
  • Corticosteroids - these are steroids and suppress inflammation. Prednisone is an example of such a drug. For cluster headache patients it is a fast-acting preventative drug. Corticosteroids may be prescribed either for patients whose symptoms are new, or those who have very long periods of remission with short-lasting cluster periods.
  • Ergotamine (Ergomar) – this medication is either placed sublingually (under the tongue) or as a rectal suppository. Patients take it at night before going to bed. This medication cannot be taken together with triptans. It should not be used for long periods or for patients with poor circulation. The drug temporarily narrows blood vessels throughout the body.
  • Anesthetic on the occipital nerve – this nerve is located at the back of the head. By numbing it, pain messages that travel along that nerve pathway are blocked. This (injectable) treatment is stopped as soon as a long-term preventative medication starts to work.
• Long-term drugs – the patient takes these throughout the cluster period. Chronic sufferers may have to take more than one long-term medication.
  • Calcium channel blockers – an example is verapamil (Calan, Verelan). After the cluster period is over the doctor will gradually taper the patient off the calcium channel blocker. For chronic sufferers long-term use may be required. Patients may experience constipation, nausea, tiredness, swollen ankles, low blood pressure (hypotension), or dizziness. Calcium channel blockers were originally prescribed for patients with heart problems; when the dose is increased the patient’s heart must be closely monitored with ECGs (electrocardiograms).
  • Lithium carbonate - an example includes Lithium (Lithobid, Eskalith). This medication is used for people with bipolar disorder, but is effective in preventing chronic cluster headaches. Patients on this medication may experience increased urination, diarrhea and tremor. The intensity of side effects is usually linked to dosage, which the doctor can alter. Patients will have regular blood tests to check for any possible kidney damage.
  • Anti-seizure medications – examples include divalproex (Depakote) and topiramate (Topamax), which are anti-seizure drugs, but also effective long-term treatments for cluster headaches.

Prevention of cluster headaches

As experts are not yet sure what the causes of cluster headaches are, it is not possible to recommend proven measures for prevention. A comprehensive preventive strategy (as mentioned above) is vital for managing the cluster headaches – simply using acute therapies is not enough.

The following may help reduce the risk of future attacks:

Alcohol - during a period when headaches occur alcohol may trigger attacks. Abstaining from alcohol during these periods will help reduce the number of headaches. Alcohol does not appear to be a trigger during periods of remission.

Inhaled nitroglycerin - this medication causes blood vessels to dilate (enlarge) and can cause headache cluster attacks. The NHS (National Health Service), UK, recommends that cluster headache sufferers avoid this medication.

Exercising in hot weather – this is a well known trigger for cluster headache. Sufferers should avoid doing anything which may cause their body’s temperature to rise rapidly.

Smoking – a significantly higher percentage of cluster headache sufferers are smokers, compared to the rest of the population. Although not proven, some suggest that giving up smoking may help.

Written by Christian Nordqvist

Copyright: Medical News Today

In addition to the insight into the normal fear response, the discovery may help to explain and perhaps even correct what goes wrong in those who suffer from panic attacks, the researchers say. (It’s been known for almost a century that carbon dioxide inhalation can trigger panic attacks, and that patients with panic disorder are particularly susceptible.)

“The amygdala has been thought of as part of the fear circuitry of the brain,” said John Wemmie of the University of Iowa, Iowa City. “Now we see it isn’t just part of a circuit, it is also a sensor.”

“It’s interesting that evolution positioned an acid sensor right in this central circuit,” added Michael Welsh, also of the University of Iowa. “Detecting an elevated carbon dioxide is critical for survival. When you are suffocating, this circuit triggers mechanisms for escape or relief of the problem.”

The circuit in question resides in the amygdala, a structure that stimulates the sympathetic nervous system for fight-or-flight and links to other brain regions involved in the response to threat. The amygdala is known from earlier studies to play a role in both innate and learned fears.

In previous studies, Wemmie’s and Welsh’s team discovered that the acid-sensing ion channel-1a (ASIC1a) is particularly abundant in the amygdala and other fear circuit structures, where it is required for normal responses in tests of fear behavior. As the name suggests, ASICs are sensitive to pH and become activated when pH levels fall.

The contribution of both the amygdala and ASIC1a to fear behavior led them to suspect that a reduced pH might induce fear behavior by activating the channels, thereby allowing the amygdala to function as a chemosensor deep within the fear circuit. And that’s exactly what they’ve now been able to show.

They found that inhaled carbon dioxide reduced brain pH and evoked fear behavior in mice. Mice breathing 5% carbon dioxide tended to avoid open spaces more than usual and, in standard tests of fear learning conducted in the presence of 10% carbon dioxide, the mice displayed exaggerated freezing behaviors.

Animals lacking those acid-sensing ion channels showed less fear, a condition that was reversed when the channels were reinstated specifically in their amygdala. Treatments that prevented the pH change reduced fear behavior, while acidic microinjections into the amygdala did just the opposite.

The new findings show that the amygdala not only senses the threat posed by carbon dioxide, but it also initiates a response. There is surely good reason for such an integrated alarm system.

“Because oxygen-breathing organisms are under a constant threat of asphyxiation, it could be argued that the threat of suffocation has had a primary influence on shaping the brain’s defensive systems,” wrote Stephen Marin of the University of Michigan, Ann Arbor in an accompanying commentary. “The present discovery that chemosensors in the amygdala are involved in generating fear responses to a variety of aversive stimuli suggests that a system that evolved to generate behavior to defend against suffocation was subsequently adapted to deal with both innate and learned threats in the external environment. In some regards, this is not surprising. In the grasp of a predator, suffocation is the ultimate fear – it signals imminent death.”

In addition to revealing the amygdala as an important chemosensor, the new results also give a molecular explanation for how rising carbon dioxide concentrations elicit intense fear and provide a foundation for dissecting the bases of anxiety and panic disorders, the researchers say. A single breath of carbon dioxide can trigger panic attacks in patients with panic disorder, they explained, and dysregulated brain pH has also been implicated in the condition. In addition, patients suffering from respiratory failure are also known to become extremely anxious.

“It has been proposed that panic and anxiety disorders involve a suffocation alarm gone haywire,” Welsh said. “Now, this work may shed some light on this well-known phenomenon and suggests strategies for further exploration.”

The findings raise the possibility that some people may be more prone to anxiety disorders, including post-traumatic stress disorder, due to genetic variants they carry in components of this ASIC pathway. They also suggest that new therapeutic strategies for panic and anxiety might target changes in brain pH or the acid-sensing channels.

The researchers include Adam E. Ziemann, University of Iowa, Iowa City, Iowa; Jason E. Allen, University of Iowa, Iowa City, Iowa; Nader S. Dahdaleh, University of Iowa, Iowa City, Iowa; Iuliia I. Drebot, University of Iowa, Iowa City, Iowa; Matthew W. Coryell, University of Iowa, Iowa City, Iowa; Amanda M. Wunsch, University of Iowa, Iowa City, Iowa; Cynthia M. Lynch, University of Iowa, Iowa City, Iowa; Frank M. Faraci, University of Iowa, Iowa City, Iowa; Matthew A. Howard III, University of Iowa, Iowa City, Iowa; Michael J. Welsh, University of Iowa, Iowa City, Iowa, Howard Hughes Medical Institute, and John A. Wemmie, University of Iowa, Iowa City, Iowa; Department of Veterans Affairs Medical Center, Iowa City, IA.

Source: Cathleen Genova
Cell Press