Discovery Of Genetic Factor In Stress Response Variability

Inherited variations in amount of an innate anxiety-reducing molecule help explain why some people can withstand stress better than others, according to a new study led by researchers at National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) , part of the National Institutes of Health ( NIH ) .

" Stress response is an important variable in vulnerability to alcohol dependence and other addictions, as well as other psychiatric disorders, " noted NIAAA Director Ting-Kai Li, M. D. " This finding could help us understand individuals' initial vulnerability to these disorders. "

Scientists led by David Goldman, M. D. , chief of NIAAA Laboratory of Neurogenetics, identified gene variants that affect expression of a signaling molecule called neuropeptide Y ( NPY ) . Found in brain and many other tissues, NPY regulates diverse functions, including appetite, weight, and emotional responses.

" NPY is induced by stress and its release reduces anxiety, " said Dr. Goldman. " Previous studies have shown that genetic factors play an important role in mood and anxiety disorders. In this study, we sought to determine if genetic variants of NPY might contribute to maladaptive stress responses that often underlie these disorders. " A report of the findings appears online in Nature.

Analyses of human tissue samples led by researchers at NIAAA identified several NPY gene variants. Collaborations with NIH-supported scientists at University of Michigan, University of Pittsburgh, University of Helsinki, University of Miami, University of Maryland, University of California at San Diego, and Yale University, showed that these variants result in a range of different effects including altered levels of NPY in brain and other tissues, and differences in emotion and emotion-induced responses of brain.

The researchers evaluated the NPY gene variants' effects on brain responses to stress and emotion. Using functional brain imaging, they found that individuals with variant that yielded lowest level of NPY reacted with heightened emotionality to images of threatening facial expressions. " Metabolic activity in brain regions involved in emotional processing increased when these individuals were presented with threatening images, " explained Doctor Goldman.

In another brain imaging experiment, people with the low level NPY variant were found to have a diminished ability to tolerate moderate levels of sustained muscular pain. Previous studies had shown that NPY's behavioral effects are mediated through interactions with opioid compounds produced by the body to help suppress pain, stress, and anxiety. " As shown by brain imaging of opioid function, these individuals released less opioid neurotransmitter in response to muscle discomfort than did individuals with higher levels of NPY, " said Doctor Goldman. " Their emotional response to pain was also higher, showing close tie between emotionality and resilience to pain and other negative stimuli. "

In a preliminary finding, the low level NPY gene variant was found to be more common than other variants among a small sample of individuals with anxiety disorders. The researchers also found that low level NPY expression was linked to high levels of trait anxiety. " Trait anxiety is an indication of an individual's level of emotionality or worry under ordinary circumstances, " explained Doctor Goldman.

The researchers conclude that these converging findings are consistent with NPY's role as an anxiety-reducing peptide and help explain inter-individual variation in resiliency to stress. " This inherited functional variation could also open up new avenues of research for other human characteristics, such as appetite and metabolism, which are also modulated by NPY, " said Doctor Goldman.

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The National Institute on Alcohol Abuse and Alcoholism, part of National Institutes of Health, is primary U. S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems and disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at http: //www. niaaa. nih. gov/.

The National Institutes of Health ( NIH ) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of U. S. Department of Health and Human Services. It is primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http: //www. nih. gov/

Source: NIAAA Press Office NIH/National Institute on Alcohol Abuse and Alcoholism

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Understanding Doxepin.

uses of Doxepin Doxepin is used to treat mental/mood problems such as depression, anxiety and bipolar disorder. It may help improve mood and feelings of well-being, relieve anxiety and tension, help we sleep better, and increase your energy level. Doxepin belongs to a class of medications called tricyclic antidepressants. It works by affecting balance of certain natural chemicals ( neurotransmitters ) in the brain.

how to use of Doxepin Read the Medication Guide available from your pharmacist. Consult your doctor or pharmacist if we have any questions.

Take Doxepin by mouth, usually 1 to 3 times daily or as directed by your doctor. If we take it only once a day, take it at bedtime to help reduce daytime sleepiness. The dosage is based on your age, medical condition and response to therapy. Your doctor may start you at a low dose and gradually increase your dose over several weeks. Follow your doctor's instructions carefully.

Use dropper that comes with medication to measure out the prescribed amount. Just before taking, mix the drug with half a glass ( 4 ounces or 120 milliliters ) of water, whole/skim milk, or orange, grapefruit, tomato, prune or pineapple juice, and drink all of mixture. Do not mix with soda or other carbonated beverages. If we are taking Doxepin in combination with liquid methadone, we may mix both drugs with lemonade, orange juice, sugar water, orange drink mix, or plain water, but not grape juice. Mix only what we need for each dose. Do not prepare a supply for future use.

Doxepin does not work right away. It may take up to 2 to 3 weeks before you experience the full benefits.

Use Doxepin regularly in order to get most benefit from it. To help we remember, take it at same times each day.

It is important to continue taking Doxepin even if you feel well. Don't suddenly stop taking Doxepin without consulting your doctor. Some conditions may become worse when the drug is abruptly stopped. Muscle aches, headaches and worsening anxiety may also occur. Your dose may need to be gradually decreased.

Tell your doctor if your condition persists or worsens.

other used of Doxepin This section contains uses of Doxepin that aren't listed in approved professional labeling for drug but that may be prescribed by your health care professional. Use Doxepin for a condition that is listed in this section only if it has been so prescribed by your health care professional.

If directed by your doctor, Doxepin may also be used to treat certain types of pain ( e. g. , peripheral neuropathy, neuropathic pain ) and trouble sleeping.

side effects of Doxepin See also Warning section.

Drowsiness, dizziness, dry mouth, blurred vision, constipation, fast heartbeat, nausea, vomiting, loss of appetite, changes in taste, weight gain, or trouble urinating may occur while use Doxepin. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

To relieve dry mouth, suck on ( sugarless ) hard candy or ice chips, chew ( sugarless ) gum, drink water, or use a saliva substitute.

Remember that your doctor has prescribed Doxepin because he or she has judged that benefit to we is greater than risk of side effects. Many people using Doxepin do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur:

Tell your doctor immediately if any of these rare but very serious side effects occur:

A very serious allergic reaction to Doxepin is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include:

This isn't a complete list of possible side effects. If we notice other effects not listed above, contact your doctor or pharmacist.

precautions of Doxepin See also Warning section.

Before taking Doxepin, tell your doctor or pharmacist if we are allergic to it, or to other tricyclic antidepressants ( e. g. , amitriptyline ) , or if you have any other allergies.

Doxepin shouldn't be used if we have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if we have:

Before using Doxepin, tell your doctor or pharmacist your medical history, especially of:

Doxepin may make we drowsy or dizzy or cause blurred vision; use caution engaging in activities requiring alertness or clear vision such as driving or using machinery. Limit alcoholic beverages.

To minimize dizziness and the risk of fainting, get up slowly when rising from a sitting or lying position.

Before having surgery, tell your doctor or dentist that we are taking Doxepin.

Doxepin may make we more sensitive to sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Wear sunblock ( SPF 30 or greater ) and a hat when outdoors.

If you have diabetes, Doxepin may increase your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if we have symptoms such as increased thirst/urination, shakiness, unusual sweating, or hunger. Your anti-diabetic medication or diet may need to be adjusted.

Depression can lead to thoughts/attempts of suicide. Tell your doctor immediately if we have any suicidal thoughts, worsening depression, or any other mental/mood changes ( including new or worsening anxiety, agitation, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, rapid speech ) . Keep all medical appointments so your doctor can monitor your progress closely and adjust your medication if needed.

Caution is advised when using Doxepin in elderly because they may be more sensitive to its side effects, especially dizziness, drowsiness, confusion, and difficulty urinating.

Caution is advised when using Doxepin in children. ( See also Warning section. ) Doxepin should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

Doxepin passes into breast milk and may have undesirable effects on a nursing infant. Breast-feeding while using Doxepin isn't recommended. Consult your doctor before breast-feeding.

interactions of Doxepin Your healthcare professionals ( e. g. , doctor or pharmacist ) may already be aware of any possible drug interactions and may be monitoring you for it. Don't start, stop or change dosage of any medicine before checking with them first.

Doxepin shouldn't be used with following medications because very serious ( possibly fatal ) interactions may occur:

Avoid taking MAO inhibitors within 2 weeks before and after treatment with Doxepin. In some cases a serious, possibly fatal drug interaction may occur while use Doxepin.

If you're currently using any of these medications listed above, tell your doctor or pharmacist before starting Doxepin.

Other drugs besides Doxepin that may affect heart rhythm ( QT prolongation in the EKG ) include disopyramide, cisapride, halofantrine, pimozide among others. Before taking Doxepin, report all medications you're currently using to your doctor or pharmacist. QT prolongation can infrequently result in serious ( rarely fatal ) fast/irregular heartbeat and other symptoms ( e. g. , severe dizziness, fainting ) that require immediate medical attention. Ask your doctor or pharmacist for more details and for instructions on how you may reduce the risk of this effect.

Before using Doxepin, tell your doctor or pharmacist of all prescription and nonprescription/herbal products we may use, especially of:

If we have been taking fluoxetine, wait at least 5 weeks after stopping fluoxetine before starting Doxepin.

Cigarette smoking decreases blood levels of this medication. Tell your doctor if we smoke or if you have recently stopped smoking.

Tell your doctor or pharmacist if we also take drugs that cause drowsiness such as:

Check labels on all your medicines ( e. g. , cough-and-cold products ) because they may contain drowsiness-causing ingredients. Ask your pharmacist about safe use of those products.

Also report use of drugs which might increase seizure risk ( decrease seizure threshold ) when combined with Doxepin such as bupropion, isoniazid ( INH ) , theophylline, or tramadol, among others. Consult your doctor or pharmacist for details.

This document doesn't contain all possible interactions. Therefore, before using Doxepin, tell your doctor or pharmacist of all products we use. Keep a list of all your medications with you, and share list with your doctor and pharmacist.

overdose of Doxepin If overdose of Doxepin is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: severe dizziness, hallucinations, fast/irregular heartbeat, fainting, widened pupils, muscle stiffness, seizures.

notes of Doxepin Don't share Doxepin with others.

Laboratory and/or medical tests ( e. g. , kidney function, Doxepin blood level ) may be performed from time to time to monitor your progress or check for side effects. Keep all medical appointments. Consult your doctor for more details.

missed dose of Doxepin If we miss a dose Doxepin, take it as soon as we remember. If it is near time of next dose, skip missed dose and resume your usual dosing schedule. Don't double dose of Doxepin to catch up.

storage of Doxepin Store Doxepin at room temperature between 59-86 degrees F ( 15-30 degrees C ) . Keep away from light and moisture. Don't store Doxepin in the bathroom. Keep all medicines away from children and pets.

Properly discard Doxepin when it's expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

warning of Doxepin Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people ( especially children/teenagers ) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. Therefore, it is very important to talk with doctor about the risks and benefits of antidepressant medication ( especially for children/teenagers ) , even if treatment isn't for a mental/mood condition. Tell doctor immediately if you notice worsening depression/other psychiatric conditions, unusual behavior changes ( including possible suicidal thoughts/attempts ) , or other mental/mood changes ( including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech ) . Be especially watchful for these symptoms when a new antidepressant is started or when dose is changed.

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