Smoking and caffeine were inversely associated with the development of Parkinson’s disease in a case-control study of families with a history of the disease, per the April Archives of Neurology. Three hundred fifty-six case subjects and 317 family controls provided a self-report of history, status, dosage, duration, and intensity of smoking, intake of coffee and total caffeine, and use of NSAIDS. Individuals with PD were nearly half as likely to report ever smoking (odds ratio [OR], 0.56) and less than one third as likely to report current smoking (OR, 0.30), compared with unaffected relatives. Increased dosage and intensity of total caffeine consumption were also inversely associated with PD (OR for high caffeine dosage, 0.58). There was no association observed between PD and use of nonsteroidal anti-inflammatory drugs.

Methamphetamine is a full agonist of the trace amine-associated receptor 1 (TAAR1), a signaling system expressed in the areas of the brain involved in drug craving, olfaction, and temperature regulation, reported researchers in the April Journal of Pharmacology and Experimental Therapeutics. In a mouse model and a human rate chimera, TAAR1 was activated by both methamphetamine and amphetamine. The authors suggested that TAAR1 could be a novel mediator of the effects of the drugs in vivo and that it could be a target for the reverse of methamphetamine’s adverse health effects and suppression of an abuser’s cravings.

Severity and frequency of symptoms of Alzheimer’s disease may predict a person’s likelihood of nursing home placement and may identify patients at increased risk for a worse prognosis, as reported in the April American Journal of Geriatric Psychiatry. One hundred twenty-two patients with Alzheimer’s disease were placed into one of three groups, based on neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory; after three years, patients in the highly symptomatic subgroup had an increased risk of nursing home placement. In addition, the Cox proportional three-year survival rates for the highly symptomatic and affective/apathetic subgroups were significantly lower than for the minimally symptomatic subgroup.

Arthritic pain was associated with increased activation of areas of the brain involved in the processing of fear and emotions and in aversive conditioning, in addition to the traditional pain matrix, according to a study in the April Arthritis and Rheumatism. Positron emission tomography measured and mapped fluorodeoxyglucose uptake in six men and six women with knee osteoarthritis during states of arthritic pain and experimental pain (induced by heat application), as well as during a pain-free control situation. Both pain conditions activated the entire pain matrix, reported the researchers; however, only the arthritic pain prompted heightened activation of the cingulate cortex, the thalamus, and the amygdala. The authors recommended that new analgesics for arthritis that act on the brain should modify this circuitry as well as the pain matrix.

Deep brain stimulation may be a viable alternative for patients with severe depression that has proven resistant to pharmacotherapy, psychotherapy, and electroconvulsive therapy, reported researchers in the online April 11 Neuropsychopharmacology. Three patients who were nonresponsive to those forms of therapy underwent implantation with bilateral deep brain stimulation electrodes in the nucleus accumbens. “Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off,” said the authors. They reported that some effects were observable immediately, and that brain metabolism, as measured by fluorodeoxyglucose–positron emission tomography, was significantly changed at one week postsurgery. No side effects aside from those directly related to the surgical procedure were observed.

Bilateral subthalamic nucleus stimulation for the treatment of Parkinson’s disease (PD) may induce pathologic gambling, reported researchers in the May Journal of Neurology, Neurosurgery, and Psychiatry. A 63-year-old man with a 10-year history of PD and no history of pathological gambling who underwent the surgery reported, after three years, that he had begun pathologic gambling one month postsurgery. Performance on tasks that measure abnormal reward processing and the weighing of immediate rewards against long-term losses were normal or at chance level. One week after neurostimulation was switched off, pathologic gambling decreased but motor impairment increased, said the researchers. The urge to gamble only “completely disappeared” after treatment with pergolide (6 to 8 mg/day) was stopped and monopolar stimulation of the most rostral contact point was restarted.

A model of amyotrophic lateral sclerosis (ALS) created with mouse embryonic stem cells has indicated that mutated astrocytes can induce motor neuron death through the release of a toxic factor, according to two studies in the online April 15 Nature Neuroscience. The first study used the model to develop co-cultures of the mutant glial cells with motor neurons carrying either the nonpathologic SOD1 transgene or the mutant SOD1(G93A); both cultures showed neurodegeneration, proving that the mutated cells have a “direct, non-cell autonomous effect on motor neuron survival.” The second study demonstrated that the toxic secretion from the mutated astrocytes will not cause the death of GABAergic or dorsal root ganglion neurons, or of embryonic stem cell-derived interneurons; in addition, the investigators reported that fibroblasts, microglia, cortical neurons, and myocytes that expressed mutated SOD1 did not cause overt neurotoxicity. Taken together, the studies’ findings indicate that an effective therapy for ALS must overcome the destructive effects of astrocytes and replace the damaged motor neurons.

Expansion of a gene that regulates DNA repair may explain the delayed onset and progression of Huntington’s disease and may point toward a target for treatment that would stop or slow the onset of disease, reported researchers in the online April 22 Nature. In mice engineered to express the human huntingtin gene with an inserted gene segment known to be large enough to cause disease, those missing the base excision repair enzyme 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1) did not display expansion of the inserted segment, or it grew far less than in mice carrying a functioning version of OGG1. However, oxidative lesions built up in the DNA without a working form of OGG1. The researchers suggested that OGG1 might also be a therapeutic target for other diseases in which oxidative lesions are believed to play a role, such as Alzheimer’s disease and Parkinson’s disease.

An automated, high-throughput series of tests for the detection of possible carriers of fragile X syndrome (FXS) was reported in the April Genetics in Medicine to be highly sensitive and specific. The researchers tested single blood samples from nearly 1,000 women who had already undergone genetic testing for FXS. Seventy-six percent of the women were determined to be heterozygous for two normal alleles in the first stage of testing; the remaining samples were then automatically forwarded to the next test. All 13 women previously known to be carriers were identified in this stage of testing as having an FMR1 mutation or premutation, yielding 100% sensitivity; however, there was one false-positive, resulting in a specificity of 99.5%.

Increases in the frequency of amphetamine and cocaine abuse may lead to an increase in the rate of hospital admissions for stroke and stroke-related mortality, reported researchers in the April Archives of General Psychiatry. They estimated that between 2000 and 2003, amphetamines, followed by cannabis and cocaine, were linked to the greatest increase in abuse. Analysis of the 1,935 persons ages 18 to 44 discharged for stroke from Texas hospitals in 2003 indicated that amphetamine abuse was significantly associated with hemorrhagic stroke (odds ratio [OR], 4.95), while cocaine abuse was significantly associated with both hemorrhagic and ischemic stroke (ORs, 2.33 and 2.03, respectively). Amphetamine abuse was also associated with a higher risk of death after hemorrhagic stroke (OR, 2.63).

The prevalence of psychiatric illness among neurology inpatients may be higher than previously reported, according to a study in the April Journal of Neurology, Neurosurgery, and Psychiatry. Of 197 patients admitted to a regional neuroscience center, 51.3% met DSM-IV criteria for one or more mental disorders, 18.7% met criteria for two or more mental disorders, and 5.1% met criteria for three or more mental disorders. The highest rates were observed for mood disorders (24.8%), delirium, dementia, and cognitive disorders (17.7%), and anxiety disorders (12.7%). The authors reported that there were no between-group differences in rates of mental illness in terms of age, sex, or whether subjects had a known neurologic diagnosis. A combination of five screening questionnaires had a sensitivity of 81.2% and a specificity of 77.1% for identifying those with a psychiatric disorder.

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—Jessica Dziedzic

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