Higher serotonin concentrations caused by selective serotonin reuptake inhibitors can trick dopamine transporters into retrieving serotonin into dopamine vesicles, according to a report in the April 7 Neuron. Investigators assessed serotonin and dopamine signaling by treating mouse brain slices with fluoxetine and other chemicals. “Immunohistochemical results and measurements using fast cyclic voltammetry showed that elevated serotonin is taken up by dopamine transporters into striatal dopamine terminals that subsequently release serotonin and dopamine together,” they said. They noted that the possibility that a certain amount of serotonin enters dopamine terminals during chronic fluoxetine treatment in childhood may contribute to the serotonin signaling responsible for depression and behavioral abnormalities seen in these patients during adulthood.

Researchers have identified two critical periods for increased risk of suicide in patients with Huntington’s disease. According to a report in the April American Journal of Psychiatry, the first critical period is immediately before a formal diagnosis of Huntington’s disease is made, and the second critical period is in stage 2 of the disease, when independence diminishes. Suicidal ideation was present in 9.1% of at-risk patients with normal neurologic examination results, 19.8% of at-risk patients with soft neurologic signs, and 23.5% of patients with possible Huntington’s disease. Among patients with a diagnosis of Huntington’s disease, 16.7% had suicidal ideation in stage 1 of the disease and 21.6% had suicidal ideation in stage 2. The researchers commented, “It is critical for health care providers to be aware of periods during which patients may be at an increased risk” of suicide.

A premorbid history of major depressive disorder seems to be associated with more severe cognitive deficits during the course of dementia. Using the Clinical Assessment of Depression in Dementia Scale, investigators screened 43 patients who had Alzheimer’s disease with mild to moderate cognitive impairment for a life-long history of major depressive disorder. They found that 22 patients had a history of major depressive disorder before onset of cognitive impairment. As a group, those with a history of major depressive disorder scored lower on cognitive performance tests—including the Mini-Mental State Examination and the Initiation/Perseveration subscale of the Mattis Dementia Rating Scale—and developed symptoms of dementia at a significantly earlier age than did subjects who had no premorbid history of major depressive disorder. The findings were reported in the April American Journal of Geriatric Psychiatry.

When comparing lisinopril with chlorthalidone, investigators observed different treatment effects by race for secondary outcomes such as blood pressure reduction, stroke, and cardiovascular disease outcomes. According to a report in the April 6 JAMA, 33,357 patients with hypertension were randomized to antihypertensive regimens initiated with amlodipine, lisinopril, or chlorthalidone to determine whether an ACE inhibitor or a calcium channel blocker is superior to a thiazide-type diuretic in reducing cardiovascular disease incidence in racial groups. The researchers found that in African-American patients, randomization to lisinopril significantly increased risk of stroke (risk ratio, 1.40), compared with randomization to chlorthalidone. No such effect was seen in non–African-American patients. Furthermore, the risk ratio for combined cardiovascular disease (coronary heart disease, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure, or peripheral vascular disease) was 1.19 for African-American patients versus 1.06 for non–African-American patients.

Ortho-McNeil Neurologics, Inc. has changed the name of Reminyl^® (galantamine HBr) to Razadyne^™ in an effort to avoid confusion with the diabetes drug Amaryl^®. The change was brought about after several reports were made indicating errors in prescribing information. Ortho-McNeil emphasized that Reminyl and Razadyne are the exact same drug and therefore should not be taken at the same time. Furthermore, the effectiveness and safety of Razadyne are equivalent to those of Reminyl. A new Web site for the drug is currently under construction.

Participating in a variety of leisure and physical activities may reduce dementia risk in older individuals, suggested a study in the April 1 American Journal of Epidemiology. A total of 3,375 men and women 65 or older were asked to fill out questionnaires about how frequently and for what duration they participated in 15 common physical activities. Results suggested that participating in a number of different activities may be as important or more important than frequency, duration, and intensity of physical activity with respect to dementia risk. Dementia occurred less frequently in patients who participated in more activities compared with those who participated in fewer activities. The association did not hold true, however, in patients with the apolipoprotein E (APOE) ε4 genotype. “We don’t know why this association exists or what causes it. It could be that maintaining a variety of activities keeps more parts of the brain active, or that this variety reflects better engagement in both physical and social activities,” said investigators.

Obesity in middle age increases the risk of dementia in later life, according to research in the April 29 online edition of BMJ. Investigators studied 10,276 patients ages 40 to 45 who underwent detailed health examinations from 1964 to 1973. They found that in 1994, dementia had been diagnosed in 713 patients. Compared with patients of normal weight, those who were obese or overweight in middle age were 74% and 35% more likely to have dementia, respectively. According to the investigators, body mass index predicted dementia more strongly in women. Obese women were 200% more likely to have dementia than women of normal weight, whereas obese men had a 30% increased risk of dementia. In addition, men and women with the highest skinfold measurements had a 60% to 70% greater risk of dementia compared with those with the lowest measurements.

High blood lead concentration is associated with lower IQ in children at an older age than previously thought, suggested a report in the May Environmental Health Perspectives. Researchers evaluated data from 780 children who had been regularly tested for blood lead concentration and had completed IQ tests at ages 2, 5, and 7. According to the researchers, the prevailing assumption is that most of the damage from lead exposure is incurred by age 2; however, results from the current study indicated that blood lead concentration had the strongest association with IQ deficits in older children. They emphasized the importance of testing for, monitoring, and reducing lead contamination in older children as well as in younger children.

Using RNA interference, investigators were able to reduce levels of the protein huntingtin (htt) in mice and significantly improve the movement and neurologic abnormalities associated with the disease. According to a report in the April 19 Proceedings of the National Academy of Sciences, htt levels were reduced to about 40% of the levels seen in untreated mice. “For a disease that takes decades to develop, a partial reduction may slow down the disease-causing copy of the gene to such an extent that either the disease progression is delayed or possibly even disease onset is prevented,” researchers said. “If the benefit is confirmed in other mouse models of Huntington’s disease, and it appears that we don’t need to target the RNA interference specifically to the disease-causing mutant gene,” testing of this approach in humans with the disease may be possible within several years, they concluded.

Cigarette smoking may contribute to the progression of multiple sclerosis (MS), according to a report in the March 9 Brain. The report detailed two studies—a nested case-control study including 201 patients with MS and 1,913 controls (to assess the association between smoking and risk of MS) and a cohort study including 179 patients with MS (to assess the association between smoking and progression of MS). Researchers found that patients who had ever smoked were 1.3 times more likely to have MS than patients who had never smoked. Furthermore, patients who had ever smoked were 3.6 times more likely to develop secondary progressive MS than patients who had never smoked. Researchers said their findings raise a number of questions, including whether or not a dose-response relation between cumulative exposure to tobacco and risk exists, how long the duration of the tobacco effect is, and whether or not second-hand smoking is associated with an increased risk.

GlaxoSmithKline announced that the FDA has approved Requip^® (ropinirole HCl) for the treatment of moderate to severe primary restless legs syndrome. The approval of Requip was supported by data from four double-blind, randomized, placebo-controlled trials involving adult patients with restless legs syndrome. In general, treatment with Requip resulted in significant improvements in International Restless Legs Syndrome Rating Scale and Clinical Global Impression–Global Improvement Scale scores. The most commonly observed adverse events associated with treatment with Requip were nausea, somnolence, vomiting, dizziness, and fatigue.

Testosterone and leuteinizing hormone levels are lower in patients with Huntington’s disease than in healthy controls, suggested a study in the April Annals of Neurology. Researchers measured plasma levels of testosterone in 42 male patients with Huntington’s disease and in 44 healthy controls. They found that testosterone and leuteinizing hormone levels were lower in patients with Huntington’s disease and that severity of illness was negatively related to testosterone levels. Furthermore, they found that low testosterone levels were associated with dementia but not with depression or psychotic features. “Clinical studies with selected Huntington’s disease patients are needed to evaluate possible beneficial effects of androgen substitution therapy on cognitive functions, depression, muscle mass and strength, general well-being, and, eventually, neuroprotective effects,” the researchers concluded.

Investigators have confirmed that a gene associated with restless legs syndrome susceptibility is located on chromosome 12q. According to a report in the April Archives of Neurology, 276 individuals from 19 families were examined to determine whether restless legs syndrome in each family was linked with markers on the same location on chromosome 12q that had previously been associated with restless legs syndrome. Investigators found that restless legs syndrome was consistent with linkage to chromosome 12q in five families. In addition, one feature, periodic leg movements during sleep, was significantly greater for affected individuals from the linked families than for affected individuals from the unlinked families. “These results support the presence of a major restless legs syndrome–susceptibility locus on chromosome 12q, which has been designated as RLS1, and also suggest that at least one additional locus may be involved in the origin of this prevalent condition,” investigators concluded.

Treatment with coenzyme Q₁₀ and vitamin E resulted in sustained improvement in mitochondrial energy synthesis and a slowing of the progression of certain clinical features in patients with Friedreich’s ataxia, according to a study in the April Archives of Neurology. Ten patients with Friedreich’s ataxia were treated with coenzyme Q₁₀ (400 mg/day) and vitamin E (2,100 IU/day) for a period of 47 months. Investigators observed a significant improvement in cardiac and skeletal muscle bioenergenetics, as well as a significant increase in fractional shortening as seen on echocardiography. Furthermore, comparison with cross-sectional data from 77 patients with Friedreich’s ataxia revealed that seven of 10 patients had better total International Cooperative Ataxia Rating Scale and kinetic scores than expected.

Minocycline reduced the severity of encephalitis, suppressed viral load in the brain, and decreased the expression of central nervous system inflammatory markers in macaques infected with simian immunodeficiency virus. According to details of the study published in the April 27 JAMA, five macaques were treated with minocycline (4 mg/day) 21 days after inoculation, while six infected macaques remained untreated. Blood and cerebrospinal fluid samples were taken on days 7, 10, 14, 21, 28, 35, 43, 56, 70, 77, and 84, and all macaques were humanely killed on day 84. Results indicated that only one of the five treated macaques showed signs of encephalitis, compared with five of the six untreated macaques; untreated macaques displayed much more evidence of physical damage to brain cells. The investigators said a multicenter clinical trial is being planned to test whether minocycline has the same effects in HIV-infected patients as it does in SIV-infected monkeys.

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