Folate in age-related disease

Folic acid and homocysteine in age-related disease

Mattson MP, Kruman II, Duan W

Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, USA

It has been known for decades that babies born to women that have a dietary deficiency in folic acid (folate) are at increased risk for birth defects, and that the nervous system is particularly susceptible to such defects.

Folate deficiency in adults can increase risk of coronary artery disease, stroke, several types of cancer, and possibly Alzheimer's and Parkinson's diseases.

Recent findings have begun to reveal the cellular and molecular mechanisms whereby folate counteracts age-related disease. An increase in homocysteine levels is a major consequence of folate deficiency that may have adverse effects on multiple organ systems during aging.

Humans with inherited defects in enzymes involved in homocysteine metabolism, including cystathionine beta-synthase and 5,10-methylenetetrahydrofolate reductase, exhibit features of accelerated aging and a marked propensity for several age-related diseases. Homocysteine enhances accumulation of DNA damage by inducing a methyl donor deficiency state and impairing DNA repair. In mitotic cells such DNA damage can lead to cancer, while in postmitotic cells such as neurons it promotes cell death.

The emerging data strongly suggest that elevated homocysteine levels increase the risk of multiple age-related diseases, and point to dietary supplementation with folate as a primary means of normalizing homocysteine levels and increasing healthspan.

Ageing Res Rev 2002 Feb;1(1):95-111

Children of drug dependent parents

Predictors of internalizing and externalizing problems among children of cocaine and opiate dependent parents

STANGER Catherine (1) ; KAMON Jody (1) ; DUMENCI Levent (1) ; HIGGINS Stephen T. (1) ; BICKEL Warren K. (1) ; GRABOWSKI John (2) ; AMASS Leslie (3) ;

(1) Department of Psychiatry, University of Vermont, 1 South Prospect Street, Burlington, VT 05401-3456, ETATS-UNIS(2) Department of Psychiatry, Houston Health Science Center, University of Texas, 1300 Moursund Ave, Suite 115, Houston, TX 77030, ETATS-UNIS(3) Friends Research Institute, Inc., 11075 Santa Monica Blvd, Suite 225, Los Angeles, CA 90025, ETATS-UNIS

We tested associations in structural models among parent individual problems (severity of drug problems, medical problems, psychiatric symptoms), family problems, and children's internalizing and externalizing problems. Results were compared for cocaine versus opiate dependent parents, mothers versus fathers, boys versus girls, and older versus younger children.

Cocaine and opiate dependent parents in treatment (N = 211) were interviewed about their substance use, psychiatric symptoms, and interpersonal problems and completed a measure of family problems.

Parents also rated children's internalizing and externalizing problems. In structural models controlling for the significant correlations between parent and family problems and between children's internalizing and externalizing problems, family problems but not individual parent problems predicted children's internalizing and externalizing symptoms. Models were similar across all groups compared with the exception of parent gender, with significant relations between parent and family problems for mothers but not for fathers.

In addition, older girls were more deviant relative to their same-age and gender peers than the younger girls and boys.

These results suggest that the personal problems of drug dependent mothers may influence children's problems indirectly by increasing family problems. For drug dependent fathers, family problems were an independent predictor of children's problems.

Drug and alcohol dependence 2002, vol. 66, no2, pp. 199-212 (1 p.1/4)

HIV vaccine:large-scale clinical trial

First large-scale HIV vaccine trial in South Africa opens

A large-scale clinical trial of a candidate HIV vaccine—which previously showed promise in smaller studies in the United States and elsewhere—has now opened in South Africa. The study plans to enroll up to 3,000 HIV-negative men and women, making it the largest African HIV vaccine trial to date.

Conducted jointly by the South African AIDS Vaccine Initiative (SAAVI) and the HIV Vaccine Trials Network (HVTN), the trial is supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The study vaccine, provided by Merck & Co. Inc. (Whitehouse Station, NJ), contains copies of only three HIV genes, not the entire virus, so it is impossible for a trial volunteer to become infected from the vaccine.

"Our best hope of ending the AIDS epidemic is a safe and effective vaccine," says NIH Director Elias A. Zerhouni, M.D. "To achieve that goal requires the concerted effort of governments, scientists and private industry as well as participation by well-informed volunteers."

"We applaud the South Africans for bringing this important trial to fruition. This international partnership exemplifies the model of collaboration needed to defeat HIV/AIDS," says NIAID Director Anthony S. Fauci, M.D.In South Africa the trial is called Phambili ("moving forward"). Also known as HVTN 503, it is a Phase IIb "test-of-concept" trial, the first such vaccine study in South Africa. This type of trial is designed to provide preliminary information on vaccine efficacy and thus enable researchers to decide whether or not to conduct a larger Phase III efficacy trial that could lead to licensure.

In smaller trials, the vaccine was found to be safe and to stimulate cellular immune responses against HIV in more than half of volunteers. To date, more than 1,800 people have received at least one injection. Two years ago, the first Phase IIb trial of the vaccine opened at sites in the United States, Canada, South America, Australia and the Caribbean (see http://www3.niaid.nih.gov/news/newsreleases/2005/mercktrial.htm), areas where a subtype of HIV called clade B predominates. That trial is ongoing.As in that study, the main objectives of HVTN 503 are to determine whether the candidate vaccine can prevent HIV infection or, in those who do become infected, lower the level of HIV early on. Additionally, the new trial will determine if the vaccine, which is based on clade B HIV, has the potential to protect against the HIV clade C subtype prevalent in South Africa. Immune responses in the first several hundred volunteers will be assessed to ensure the vaccine induces promising immune responses in this population against the clade C virus before proceeding to full enrollment.

Study volunteers must be healthy, sexually active, HIV-negative men and women, ages 18 to 35 years old. Investigators will assign them at random to receive either the test vaccine or an inactive placebo injection. The trial is double-blind, meaning that neither the researchers nor the volunteers know which a participant has received. All volunteers will be regularly counseled about ways to reduce their risk of acquiring HIV, and they will be given condoms. Access to care and treatment for sexually transmitted infections will be provided, and because recent findings indicate that medical circumcision can reduce the risk of HIV transmission from women to men, access to medical circumcision will also be provided to male participants who desire it.

In South Africa, the trial is led by Glenda Gray, MBBCH, FCPaeds (SA), of the Perinatal HIV Research Unit, University of the Witwatersrand, based at the Chris Hani Baragwanath Hospital in Soweto. James Kublin, M.D., M.P.H., of Fred Hutchinson Cancer Research Center, Seattle, serves as study co-chair. The study is expected to recruit volunteers at five sites in South Africa, located in Soweto, Cape Town, Klerksdorp, Medunsa and Durban.According to Dr. Gray, the study team has actively sought community endorsement of and support for this clinical trial, both of which are critical to its success. "Our communities here in South Africa are faced with the burden of HIV on a daily basis, and the trial investigators and study team have spent years developing a rapport with the community so that together we can move forward in our quest to identify improved approaches to prevent new HIV infections."

The test vaccine contains a weakened adenovirus that serves as a carrier for three clade B HIV genes. Adenoviruses are among the main causes of upper respiratory tract ailments such as the common cold. Because the vaccine contains only three HIV genes housed in weakened adenoviruses, study participants cannot become infected with HIV or get a respiratory infection from the vaccine. The study aims to determine if the HIV genes will induce a cellular immune response, producing immune cells that recognize and kill cells infected with HIV.

The South African Medicines Control Council, the South African Department of Agriculture and the U.S. Food and Drug Administration have reviewed the trial and allowed the study to proceed. In order to conduct the trial, sites also are required to obtain institutional ethics and biosafety committee approvals.

NIH/National Institute of Allergy and Infectious Diseases

Sick Building Syndrome: epidemiological study

Building health: an epidemiological study of "sick building syndrome" in the Whitehall II study

A F Marmot1, J Eley1, M Stafford2, S A Stansfeld3, E Warwick2 and M G Marmot2
1) AMA, Linton House, London, UK; 2) Department of Epidemiology and Public Health, University College London Medical School, London, UK; 3) Centre for Psychiatry, Barts and the London, Queen Mary’s School of Medicine and Dentistry, Medical Sciences Building, London, UK

Objectives: Sick building syndrome (SBS) is described as a group of symptoms attributed to the physical environment of specific buildings. Isolating particular environmental features responsible for the symptoms has proved difficult. This study explores the role and significance of the physical and psychosocial work environment in explaining SBS.

Methods: Cross sectional data on the physical environment of a selection of buildings were added to individual data from the Whitehall II study—an ongoing health survey of office based civil servants. A self-report questionnaire was used to capture 10 symptoms of the SBS and psychosocial work stress. In total, 4052 participants aged 42–62 years working in 44 buildings were included in this study.

Results: No significant relation was found between most aspects of the physical work environment and symptom prevalence, adjusted for age, sex, and employment grade. Positive (non-significant) relations were found only with airborne bacteria, inhalable dust, dry bulb temperature, relative humidity, and having some control over the local physical environment. Greater effects were found with features of the psychosocial work environment including high job demands and low support. Only psychosocial work characteristics and control over the physical environment were independently associated with symptoms in the multivariate analysis.

Conclusions: The physical environment of office buildings appears to be less important than features of the psychosocial work environment in explaining differences in the prevalence of symptoms.
Keywords: sick building syndrome; office environment; psychosocial work characteristics

Occupational and Environmental Medicine 2006;63:283-289;
© 2006 by BMJ Publishing Group Ltd

Girls' depression

Young adolescent girls' depression is tied to more stressful life events

Children's conduct problems—skipping school, sneaking out of the house, lying to parents, shoplifting, or bullying other children—are a major source of concern for parents and teachers. As a potential cause of these problems, parents' marital conflict has received a lot of research attention. Now a new study finds that parents' fighting may not be to blame but rather that parents who argue a lot may pass on genes for disruptive behavior to their children.

A group of researchers from the University of Virginia and several other universities looked at this question, studying 1,045 twins and their 2,051 children. Some of the parents were identical twins and shared all of their genes and some were fraternal and shared only half of their genes.

The study found that parents' fighting is not likely a cause of children's conduct problems. On the other hand, parents' genes influenced how often they argued with their spouses and these same genes, when passed to their children, caused more conduct problems.

"This study suggests that marital conflict is not a major culprit, but genes are," said K. Paige Harden, the lead researcher and professor of psychology at the University of Virginia. "Our findings have potential implications for treating conduct problems: Focusing on a child's parents, as is common in family therapy, may not be as effective as focusing on the child.

"The study was supported, in part, by grants from the National Institute on Alcohol Abuse and Alcoholism and the National Alliance for Research on Schizophrenia and Depression.

The findings are published in the January/February 2007 issue of the journal Child Development.

Society for Research in Child Development

Passive smoke

Passive smoke in workplace increases lung cancer risk

An analysis of nearly two dozen studies confirms the association between passive smoke in the workplace and an increased risk of lung cancer, according to a report in the American Journal of Public Health.

Stayner and colleagues conducted a statistical analysis combining data from 22 studies evaluating workplace smoking exposure and lung cancer risk. They also analyzed workers' level and duration of exposure to passive smoke and their risk of lung cancer.

The researchers found a 24 percent increase in lung cancer risk among people exposed to passive smoke in the workplace. Workers who were highly exposed had a 100 percent increased (or doubled) risk of lung cancer, and workers with a long history, or duration, of exposure to passive smoke had a 50 percent increased risk.

"We believe this provides the strongest evidence to date of the relationship between workplace environmental tobacco smoke and lung cancer," said Stayner, professor and director of epidemiology and biostatistics at the UIC School of Public Health, and lead author of the study.

The research, Stayner said, has important policy implications for cities and states that have not yet legislated smoking bans in bars and restaurants where there are high levels of environmental smoke.

University of Illinois at Chicago

Cough: Antibiotic treatment

Antibiotics for whooping cough (pertussis).

Altunaiji S, Kukuruzovic R, Curtis N, Massie J.Zayed
Military Hospital, Zayed Street, PO Box 3740, Abu Dhabi, UNITED ARAB EMIRATES.

BACKGROUND: Whooping cough is a highly contagious disease. Infants are the population at highest risk of severe disease and death. Erythromycin for 14 days is recommended for treatment and contact prophylaxis but this regime is considered inconvenient and prolonged. The value of contact prophylaxis is uncertain.

OBJECTIVES: To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough.

SELECTION CRITERIA: All randomised and quasi-randomised controlled trials of antibiotics for treatment of and contact prophylaxis against whooping cough were included in the systematic review.

DATA COLLECTION AND ANALYSIS: At least three reviewers independently extracted data and assessed the quality of each trial.

MAIN RESULTS: Twelve trials with 1,720 participants met the inclusion criteria. Ten trials investigated treatment regimens and two investigated prophylaxis regimens. The quality of the trials was variable. Results showed that short-term antibiotics (azithromycin for three days, clarithromycin for seven days, or erythromycin estolate for seven days) were equally effective with long-term antibiotic treatment (erythromycin estolate or erythromycin for 14 days) in the microbiological eradication of Bordetella pertussis (B. pertussis) from the nasopharynx. The relative risk (RR) was 1.02 (95% confidence interval (CI) 0.98 to 1.05). Side effects were fewer with short-term treatment (RR 0.66; 95% CI 0.52 to 0.83). There were no differences in clinical improvement or microbiological relapse between short and long-term treatment regimens. Contact prophylaxis (of contacts older than six months of age) with antibiotics did not significantly improve clinical symptoms or the number of cases that developed culture positive B. pertussis.

AUTHORS' CONCLUSIONS: Antibiotics are effective in eliminating B. pertussis from patients with the disease, rendering them non-infectious, but do not alter the subsequent clinical course of the illness. Effective regimens include: three days of azithromycin, seven days of clarithromycin, seven or 14 days of erythromycin estolate, and 14 days of erythromycin ethylsuccinate. Considering microbiological clearance and side effects, three days of azithromycin or seven days of clarithromycin are the best regimens. Seven days of trimethoprim/sulfamethoxazole also appeared to be effective for the eradication of B. pertussis from the nasopharynx and may serve as an alternative antibiotic treatment for patients who cannot tolerate a macrolide. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

Cochrane Database Syst Rev. 2005 Jan 25;(1):CD004404.

Happy Valentine's Day!

Folate and mecobalamin: Treatment at the stroke

Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial.

Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K.
Department of Neurology, Mitate Hospital, Tagawa, Japan.

CONTEXT: Stroke increases the risk of subsequent hip fracture by 2 to 4 times. Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly men and women. Treatment with folate and mecobalamin (vitamin B12) may improve hyperhomocysteinemia.

OBJECTIVE: To investigate whether treatment with folate and vitamin B12 reduces the incidence of hip fractures in patients with hemiplegia following stroke.

DESIGN, SETTING, AND PATIENTS: A double-blind, randomized controlled study of 628 consecutive patients aged 65 years or older with residual hemiplegia at least 1 year following first ischemic stroke, who were recruited from a single Japanese hospital from April 1, 2000, to May 31, 2001. Patients were assigned to daily oral treatment with 5 mg of folate and 1500 microg of mecobalamin, or double placebo; 559 completed the 2-year follow-up.

MAIN OUTCOME MEASURE: Incidence of hip fractures in the 2 patient groups during the 2-year follow-up.

RESULTS: At baseline, patients in both groups had high levels of plasma homocysteine and low levels of serum cobalamin and serum folate. After 2 years, plasma homocysteine levels decreased by 38% in the treatment group and increased by 31% in the placebo group (P<.001). The number of hip fractures per 1000 patient-years was 10 and 43 for the treatment and placebo groups, respectively (P<.001). The adjusted relative risk, absolute risk reduction, and the number needed to treat for hip fractures in the treatment vs placebo groups were 0.20 (95% confidence interval [CI], 0.08-0.50), 7.1% (95% CI, 3.6%-10.8%), and 14 (95% CI, 9-28), respectively. No significant adverse effects were reported.

CONCLUSION: In this Japanese population with a high baseline fracture risk, combined treatment with folate and vitamin B12 is safe and effective in reducing the risk of a hip fracture in elderly patients following stroke.

JAMA. 2005 Mar 2;293(9):1082-8.

Medication therapies for migraine

Anti-Migraine agents

A migraine headache is a form of vascular headache. Migraine headache is caused by a combination of vasodilatation (enlargement of blood vessels) and the release of chemicals from nerve fibers that coil around the blood vessels. During a migraine attack, the temporal artery enlarges. (The temporal artery is an artery that lies on the outside of the skull just under the skin of the temple.) Enlargement of the temporal artery stretches the nerves that coil around the artery and causes the nerves to release chemicals. The chemicals cause inflammation, pain, and further enlargement of the artery. The increasing enlargement of the artery magnifies the pain.

Migraine attacks commonly activate the sympathetic nervous system in the body. The sympathetic nervous system is often thought of as the part of the nervous system that controls primitive responses to stress and pain, the so-called "fight or flight" response. The increased sympathetic nervous activity in the intestine causes nausea, vomiting, and diarrhea. Sympathetic activity also delays emptying of the stomach into the small intestine and thereby prevents oral medications from entering the intestine and being absorbed. The impaired absorption of oral medications is a common reason for the ineffectiveness of medications taken to treat migraine headaches. The increased sympathetic activity also decreases the circulation of blood, and this leads to pallor of the skin as well as cold hands and feet. The increased sympathetic activity also contributes to the sensitivity to light and sound sensitivity as well as blurred vision.

Migraine afflicts 28 million Americans, with females suffering more frequently (17%) than males (6%). Missed work and lost productivity from migraine create a significant public burden. Nevertheless, migraine still remains largely undertreated and underdiagnosed. Less than half the sufferers are diagnosed by their doctors.

Medication therapies for migraine

Individuals with occasional mild migraine headaches that do not interfere with daily activities usually medicate themselves with over-the-counter (OTC, non-prescription) pain relievers (analgesics). Many OTC analgesics are available. OTC analgesics have been shown to be safe and effective for short-term relief of headache (as well as muscle aches, pains, menstrual cramps , and fever) when used according to the instructions on their labels.

There are two major classes of OTC analgesics: acetaminophen (Tylenol) and non-steroidal anti-inflammatory drugs (NSAIDs). The two types of NSAIDs are aspirin and non-aspirin. Examples of non-aspirin NSAIDs are ibuprofen (Advil, Nuprin, Motrin IB, and Medipren) and naproxen (Aleve). Some NSAIDs are available by prescription only. Prescription NSAIDs are usually prescribed to treat arthritis and other inflammatory conditions such as bursitis, tendonitis, etc. The difference between OTC and prescription NSAIDs may only be the amount of the active ingredient contained in each pill. For example, OTC naproxen (Aleve) contains 220 mg of naproxen per pill, whereas prescription naproxen (Naprosyn) contains 375 or 500 mg of naproxen per pill.

Acetaminophen reduces pain and fever by acting on pain centers in the brain. Acetaminophen is well tolerated and generally is considered easier on the stomach than NSAIDs. However, acetaminophen can cause severe liver damage in high (toxic) doses or if used on a regular basis over extended periods of time. In individuals who regularly consume moderate or large amounts of alcohol, acetaminophen can cause serious damage to the liver in lower doses that usually are not toxic. Acetaminophen also can damage the kidneys when taken in large doses. Therefore, acetaminophen should not be taken more frequently or in larger doses than recommended on the label. For information, please read the Acetaminophen and Liver Damage article.

NSAIDs relieve pain by reducing the inflammation that causes the pain (They are called non-steroidal anti-inflammatory drugs or NSAIDs because they are different from corticosteroids such as prednisone, prednisolone, and cortisone which also reduce inflammation). Corticosteroids, though valuable in reducing inflammation, have predictable and potentially serious side effects, especially when used long-term. NSAIDs do not have the same side effects that corticosteroids have.

Aspirin, Aleve, Motrin, and Advil all are NSAIDs and are similarly effective in relieving pain and fever. The main difference between aspirin and non-aspirin NSAIDs is their effect on platelets. Platelets are small particles in the blood that cause blood clots to form. Aspirin prevents the platelets from forming blood clots. Therefore, aspirin can increase bleeding by preventing blood from clotting though it also can be used therapeutically to prevent clots from causing heart attacks and strokes. The non-aspirin NSAIDs also have anti-platelet effects, but their anti-platelet action does not last as long as aspirin.Aspirin, acetaminophen, and caffeine also are available combined in OTC analgesics for the treatment of headaches. Examples of such combination analgesics are Pain-aid, Excedrin, Fioricet, and Fiorinal.

Finding an effective analgesic or analgesic combination often is a process of trial and error because individuals respond differently to different analgesics. In general, a person should use the analgesic that has worked in the past. This will increase the likelihood that an analgesic will be effective and decrease the risk of side effects.

What is PMDD

PMDD stands for Premenstrual Dysphoric Disorder. It's a severe form of PMS (Premenstrual Syndrome). Like PMS, PMDD occurs the week before the onset of menstruation and disappears a few days after. PMDD is characterized by severe monthly mood swings and physical symptoms that interfere with everyday life, especially a woman's relationships with her family and friends. PMDD symptoms go far beyond what are considered manageable or normal premenstrual symptoms.

PMDD is a combination of symptoms that may include irritability, depressed mood, anxiety, sleep disturbance, difficulty concentrating, angry outbursts, breast tenderness and bloating. The diagnostic criteria emphasize symptoms of depressed mood, anxiety, mood swings or irritability. The condition affects up to one in 20 American women who have regular menstrual periods.

Among 500 women recently surveyed, eight out of ten did not know that severe premenstrual problems have been officially classified as PMDD, nor did they know that such problems can be diagnosed and treated. Even more disturbing is that the one in four respondents who described their premenstrual symptoms as strong or severe were among those unaware of PMDD.

Twenty to fifty percent of women between the ages of 30 to 40 with regular menstrual cycles experience premenstrual syndrome (PMS) as a regular physiological occurrence every month. In more severe cases, affecting three to five percent of menstruating women, this syndrome is labeled as premenstrual dysphoric disorder (PMDD) . Patients with severe PMDD may be at risk for developing postpartum depression. Furthermore, women successfully treated with antidepressants often show breakthrough symptoms of depression in the premenstrual phase of their menstrual cycle. All that is needed is a small increase in the dosage of the antidepressant premenstrually.

PMDD Symptoms

Women with PMDD complain of irritability, anger, tension, marked depressed mood, and mood liability (crying spells for no reason), verbal outbursts, to such a severity that quality of life is seriously compromised. In addition to these symptoms, some women complain of exhaustion, fatigue, sleep disturbance, limited concentration and a host of physical symptoms such as breast tenderness, headaches, joint and muscle pain, bloating and weight gain.

The primary symptoms that distinguish premenstrual dysphoric disorder from other mood disorders (i.e., major depression) or menstrual conditions is the onset and duration of PMDD symptoms -- with symptoms appearing during the week or so before and disappearing within a few days after the onset of menses -- and the level by which these symptoms disrupt daily living tasks. (This diminished level of functioning is generally in great contrast with the same woman's interactions and abilities at other times during the month.)

The symptoms of PMDD may resemble other conditions or medical problems, such as a thyroid condition, depression, or an anxiety disorder. Consult a physician for diagnosis.

What Causes PMDD?
Although the exact cause of PMDD is not known, several theories exist. No one knows for sure, but it may be related to the neurotransmitter in the brain called serotonin (sair – uh – toe – nin). The symptoms of PMDD may occur when serotonin and other neurotransmitters are out of balance. In PMDD, this imbalance may be related to your monthly changes in hormones.
One theory states that women who experience PMDD may have abnormal reactions to normal hormone changes that occur with each menstrual cycle. This may include the fluctuation of estrogen and progesterone levels that normally occur with menstruation causing a serotonin deficiency, in some women (Serotonin is a substance found naturally in the brain and intestines that acts as a vessel-narrowing substance, or vasoconstrictor). Additional research is necessary.

How is Premenstrual Dysphoric Disorder Diagnosed?

Aside from a complete medical history and physical and pelvic examination, diagnostic procedures for PMDD are currently very limited. Your physician may consider recommending a psychiatric evaluation to, more or less, provide a differential diagnosis (to rule out other possible conditions). In addition, he/she may ask that you keep a journal or diary of your symptoms for several months, to better assess the timing, severity, onset, and duration of symptoms. In general, in order for a PMDD diagnosis to be made, the following symptoms must be present:

Over the course of a year, during most menstrual cycles, five or more of the following symptoms must be present:

* depressed mood

* anger or irritability

* difficulty in concentrating

* lack of interest in activities once enjoyed

* moodiness

* increased appetite

* insomnia or hypersomnia

* feeling overwhelmed or out of control

* symptoms that disturb social, occupational, or physical functioning

* symptoms that are not related to, or exaggerated by, another medical condition.

PMDD Treatment

Treatment for PMS depends on the severity of the symptoms. For mild cases, treatment recommendations include diet modifications such as high carbohydrate meals and reducing salt, caffeine and alcohol, as well as a variety of methods for stress reduction and relaxation such as exercise, counseling and stress/behavior management strategies.

For severe PMDD, treatment is more aggressive, often requiring pharmacological intervention in addition to nonpharmacological treatments. The selective serotonin reuptake inhibitor class of antidepressants are effective in the treatment of PMDD. Fluoxetine (Prozac - Serafem) has been widely studied and found to be effective in reducing symptoms of tension, irritability and dysphoria. These results have been replicated with sertraline (Zoloft) and paroxetine (Paxil). Use of the SSRIs is positive as well in that side effects, such as nausea, diarrhea, headache, and insomnia, to name a few, are minimal and reportedly tolerable by the majority of women.

For some women, even more drastic measures must be taken to ameliorate the symptoms of PMDD. For these women, hormonal therapies are necessary that work by suppressing the menstrual cycle. For some women, the severity of symptoms increase over time and last until menopause (when menses ceases). For this reason, a woman may require treatment for an extended period of time, and may require several re-evaluations to adjust medication dosages throughout the course of treatment.

Women, however, do face barriers to diagnosis and treatment. There is often a stigma attached to any condition that is associated with the menstrual cycle. Many women who do not seek treatment for the mood and physical symptoms of PMDD accept their symptoms as an inevitable consequence of the menstrual cycle which cannot be addressed.Some women view seeking treatment for PMDD as a sign of weakness. Additionally, physicians aren't traditionally trained to recognize the signs and symptoms of PMDD symptoms are often dismissed as just a "part of being a woman." This attitude often keeps women from getting the help they need.If you think you have PMDD find a doctor is familiar with PMDD or get a second opinion from another OB/GYN or psychiatrist.

http://www.coolnurse.com/pmdd.htm

Children of cocaine- and opiate-dependent parents

Behavioral and emotional problems among children of cocaine- and opiate-dependent parents

STANGER C. (1) ; HIGGINS S. T. (1) ; BICKEL W. K. (1) ; ELK R. (2) ; GRABOWSKI J. (2) ; SCHMITZ J. (2) ; AMASS L. (3) ; KIRBY K. C. (4) ; SERACINI A. M. (5) ;
1) Department of Psychiatry, University of Vermont, Burlington, ETATS-UNIS ; 2) Department of Psychiatry, University of Texas, Houston, ETATS-UNIS ; 3) Department of Psychiatry, University of Colorado, Denver, ETATS-UNIS ; 4) Counseling Psychology Program, Temple University, Philadelphia, ETATS-UNIS ; 5) Department of Psychiatry, Columbia University, New York, ETATS-UNIS

Objective: To test associations between parental drug abuse and children's problems, children of cocaine- and opiate-dependent parents were compared with demographically matched referred and nonreferred children.

Method: Cocaine-and opiate-dependent parents in treatment completed the Child Behavior Checklist for 410 children (218 boys, 192 girls) from ages 2 through 18 years (mean = 7.9 years). Children of drug abusers (CDAs) were demographically matched to referred (RCs) and nonreferred children (NRCs).

Results: RCs scored lower than CDAs and NRCs on most competence scales, and higher than CDAs and NRCs on all problem scales. CDAs scored lower than NRCs on most competence scales, and higher than NRCs on Withdrawn, Thought Problems, Delinquent Behavior, Aggressive Behavior, Internalizing, Externalizing, and Total Problems. Group status also predicted clinical range scores on most competence and all problem scales.
Conclusions: Children of drug abusers showed more internalizing and externalizing psychopathology relative to matched nonreferred children, but they showed significantly less psychopathology than shown by matched referred children. Children of drug abusers are an important group to target for preventive interventions.

J. Am. Acad. Child Adolesc. Psych. 1999, vol. 38, №4, pp. 421-428

Types of Depression

Types of Depression in Children and Adolescents

Bipolar Disorder
Although rare in young children, bipolar disorder—also known as manic-depressive illness—can appear in both children and adolescents. Bipolar disorder, which involves unusual shifts in mood, energy, and functioning, may begin with either manic, depressive, or mixed manic and depressive symptoms. It is more likely to affect the children of parents who have the disorder. Twenty to 40 percent of adolescents with major depression develop bipolar disorder within 5 years after depression onset.

Existing evidence indicates that bipolar disorder beginning in childhood or early adolescence may be a different, possibly more severe form of the illness than older adolescent- and adult-onset bipolar disorder. When the illness begins before or soon after puberty, it is often characterized by a continuous, rapid-cycling, irritable, and mixed symptom state that may co-occur with disruptive behavior disorders, particularly attention deficit hyperactivity disorder (ADHD) or conduct disorder (CD), or may have features of these disorders as initial symptoms. In contrast, later adolescent- or adult-onset bipolar disorder tends to begin suddenly, often with a classic manic episode, and to have a more episodic pattern with relatively stable periods between episodes. There is also less co-occurring ADHD or CD among those with later onset illness.

Bipolar Disorder: Manic Symptoms
Severe changes in mood—either extremely irritable or overly silly and elated
Overly-inflated self-esteem; grandiosity
Increased energy
Decreased need for sleep—able to go with very little or no sleep for days without tiring
Increased talking—talks too much, too fast; changes topics too quickly; cannot be interrupted
Distractibility—attention moves constantly from one thing to the next
Hypersexuality—increased sexual thoughts, feelings, or behaviors; use of explicit sexual language
Increased goal-directed activity or physical agitation
Disregard of risk—excessive involvement in risky behaviors or activities
A child or adolescent who appears to be depressed and exhibits ADHD-like symptoms that are very severe, with excessive temper outbursts and mood changes, should be evaluated by a psychiatrist or psychologist with experience in bipolar disorder, particularly if there is a family history of the illness. This evaluation is especially important since psychostimulant medications, often prescribed for ADHD, may worsen manic symptoms. There is also limited evidence suggesting that some of the symptoms of ADHD may be a forerunner of full-blown mania.

The essential treatment of bipolar disorder in adults involves the use of appropriate doses of mood stabilizing medications, typically lithium and/or valproate, which are often very effective for controlling mania and preventing recurrences of manic and depressive episodes. Treatment of children and adolescents diagnosed with bipolar disorder is based mainly on experience with adults, since as yet there is very limited data on the safety and efficacy of mood stabilizing medications in youth. Researchers currently are evaluating both pharmacological and psychosocial interventions for bipolar disorder in young people.

Bipolar Disorder: A Warning About Antidepressants and Psychostimulants
Using antidepressant medication to treat depression in a person who has bipolar disorder may induce manic symptoms if it is taken without a mood stabilizer, such as lithium or valproate. In addition, using psychostimulant medications to treat ADHD or ADHD-like symptoms in a child or adolescent with bipolar disorder may worsen manic symptoms. While it can be hard to determine which young patients will become manic, there is a greater likelihood among children and adolescents who have a family history of bipolar disorder. If manic symptoms develop or markedly worsen during antidepressant or stimulant use, a child psychiatrist should be consulted, and treatment for bipolar disorder should be considered. Physicians should be aware of the signs and symptoms of mania so that they can educate families on how to recognize these and report them immediately.

National Institute of Mental Health

Prenatal cocaine: lower full scale IQ

STUDY EXAMINES EFFECTS OF PRENATAL COCAINE EXPOSURE AND INFLUENCE OF HOME ENVIRONMENT ON CHILDREN'S IQ SCORES

A study in the May 26 issue of the Journal of the American Medical Association (JAMA) suggests that prenatal cocaine exposure was not associated with lower full scale IQ scores, or verbal or performance IQ scores at age 4 years. However, the study also found that prenatal cocaine exposure was associated with specific cognitive impairments and a lower likelihood of an above average IQ, but that home environments could make a difference for better outcomes for some children.

"Cocaine readily crosses the placental and fetal brain barriers and has a direct effect on the developing fetal brain..." the authors provide as background information in the article. The authors add that "a number of methodologically sound studies have found a relationship between fetal cocaine exposure and negative child developmental outcomes in the first years of life, although others have not."

In this study, Lynn T. Singer, Ph.D., from Case Western Reserve University, Cleveland, and colleagues assessed the effects of prenatal cocaine exposure and the quality of the caregiving environment on cognitive outcomes. The participants included 376 children (190 cocaine-exposed and 186 non-exposed) from a high-risk population who were enrolled in a longitudinal study from birth (September 1994 - June 1996). They were screened for drug exposure as infants, assessed at 6, 12 and 24 months of age and then tested at 4 years old for cognitive developments.

The researchers found that prenatal cocaine exposure was not related to lower full-scale IQ scores (cocaine exposed 80.7 vs. nonexposed 82.9), summary verbal (cocaine exposed 79.9 vs. nonexposed 81.9) or performance IQ measures (cocaine exposed 85.5 vs. nonexposed 87.5) at age 4 years. "However, there were specific effects of prenatal cocaine exposure on several subscales, with cocaine-exposed children having lower information, arithmetic, and object assembly scores than nonexposed children," the researchers report. "Prenatal cocaine exposure was also associated with a lower likelihood of achievement of IQ above normative means."

The researchers continue, "Comparisons indicated that cocaine-exposed children in foster or adoptive care lived in more stimulating home environments and their caregivers had better vocabulary scores than those of cocaine-exposed children in biological maternal or relative care and nonexposed children. In addition, cocaine-exposed children in foster or adoptive care had verbal, performance, and full-scale IQs equivalent to nonexposed children, while cocaine-exposed children in biological maternal or relative care had lower full-scale and performance IQ scores than nonexposed children, despite the fact that children in foster or adoptive care had twice the severity of cocaine exposure as measured by maternal report of the average numbers of 'rocks' of cocaine used weekly over the pregnancy. Moreover, the duration of placement in foster or adoptive care was positively related to full-scale IQ," the authors note.

"These findings indicate that prenatal cocaine exposure is associated with an increased risk for specific cognitive impairments and a lower likelihood of above average IQ at 4 years of age. In addition, our findings underscore the beneficial effects of environmental intervention in the prevention of mental retardation for cocaine-exposed children. Drug treatment and education for this population of pregnant women, along with intensive intervention for their offspring, are essential to help maximize the future well-being of these families," the authors conclude.

JAMA. 2004;291:2448-2456.
Available post-embargo at jama.com

Women: antidepressant response

A comparison of antidepressant response in younger and older women.

Grigoriadis S, Kennedy SH, Bagby RM.
University Health Network, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada

The objective of this report is to compare antidepressant response rates and tolerability in younger and older women. One hundred fifteen female outpatients who met DSM-IV criteria for major depressive disorder were evaluated before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor, nefazodone, or venlafaxine. The sample was divided into younger and older groups based on age to approximate premenopausal and postmenopausal status. Eighty-six age-matched male outpatients formed the comparison group. Younger women compared with older women had significantly lower Hamilton Rating Scale for Depression scores after 8 weeks of antidepressant treatment and achieved significant higher rates of remission. There were no differences in overall drug tolerability. This pattern was not replicated in the male patients. Younger women with depression are more responsive to serotonergic antidepressants. This may relate to changes in menstrual status. Limitations of the study and implications for the role of female sex hormones are discussed. Future investigations should include measurement of reproductive hormone levels.

J Clin Psychopharmacol. 2003 Aug;23(4):405-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12920418

Prenatal cocaine exposure: behavior of children

Teacher-Assessed Behavior of Children Prenatally Exposed to Cocaine

Delaney-Black V, Covington C, Templin T, Ager J, Nordstrom-Klee B, Martier S, Leddick L, Czerwinski RH, Sokol RJ
Department of Pediatrics, School of Medicine, Wayne State University.

Objective. Prenatal cocaine exposure has been associated with alterations in neonatal behavior and more recently a dose-response relationship has been identified. However, few data are available to address the long-term behavioral effects of prenatal exposures in humans. The specific aim of this report is to evaluate the school-age behavior of children prenatally exposed to cocaine.

Methods. All black non-human immunodeficiency virus-positive participants in a larger pregnancy outcomes study who delivered singleton live born infants between September 1, 1989 and August 31, 1991 were eligible for study participation. Staff members of the larger study extensively screened study participants during pregnancy for cocaine, alcohol, cigarettes, and other illicit drugs. Prenatal drug exposure was defined by maternal history elicited by structured interviews with maternal and infant drug testing as clinically indicated. Cocaine exposure was considered positive if either history or laboratory results were positive. Six years later, 665 families were contacted; 94% agreed to participate. The child, primary caretaker (parent), and, when available, the biologic mothers were tested in our research facilities. Permission was elicited to obtain blinded teacher assessments of child behavior with the Achenbach Teacher's Report Form (TRF). Drug use since the child's birth was assessed by trained researchers using a structured interview.

Results. Complete laboratory and teacher data were available for 499 parent-child dyads, with a final sample size for all analyses of 471 (201 cocaine-exposed) after the elimination of mentally retarded subjects. A comparison of relative Externalizing (Aggressive, Delinquent) to Internalizing (Anxious/Depressed, Withdrawn, Somatic Complaints) behaviors of the offspring was computed for the TRF by taking the difference between the 2 subscales to create an Externalizing-Internalizing Difference (T. M. Achenbach, personal communication, 1998). Univariate comparisons revealed that boys were significantly more likely to score in the clinically significant range on total TRF, Externalizing-Internalizing, and Aggressive Behaviors than were girls. Children prenatally exposed to cocaine had higher Externalizing-Internalizing Differences compared with controls but did not have significantly higher scores on any of the other TRF variables. Additionally, boys prenatally exposed to cocaine were twice as likely as controls to have clinically significant scores for externalizing (25% vs 13%) and delinquent behavior (22% vs 11%). Gender, prenatal exposures (cocaine and alcohol), and postnatal risk factors (custody changes, current drug use in the home, child's report of violence exposure) were all related to problem behaviors. Even after controlling for gender, other prenatal substance exposures, and home environment variables, cocaine-exposed children had higher Externalizing-Internalizing Difference scores. Prenatal exposure to alcohol was associated with higher total score, increased attention problems, and more delinquent behaviors. Prenatal exposure to cigarettes was not significantly related to the total TRF score or any of the TRF subscales. Postnatal factors associated with problem behaviors included both changes in custody status and current drug use in the home. Change in custody status of the cocaine-exposed children, but not of the controls, was related to higher total scores on the TRF and more externalizing and aggressive behaviors. Current drug use in the home was associated with higher scores on the externalizing and aggressive subscales.

Conclusions. Results of this study suggest gender-specific behavioral effects related to prenatal cocaine exposure. Prenatal alcohol exposure also had a significant impact on the TRF. Postnatal exposures, including current drug use in the home and the child's report of violence exposure, had an independent effect on teacher-assessed child behavioral problems. Furthermore, among the children prenatally exposed to cocaine, change in the child's custody status was a significant predictor of TRF scores. It remains possible that other unmeasured postnatal characteristics of the cocaine-using household may play important roles in teacher-assessed child behavior.

Pediatrics 2000 Oct; 106(4):782-791

http://cocaine.org/longterm/kids.html