Early Characteristics in Huntington’s Disease
Duffet al. (pages 1341–1346) found that healthy individuals who have the abnormality in the Huntington gene that causes Huntington’s disease (HD) report more psychiatric symptoms (e.g., depression, anxiety, obsessive–compulsiveness) and movement-related symptoms than individuals without this genetic abnormality. The authors suggest that psychiatric symptoms may be the first signs of HD.
Huntington’s disease is a heritable neurodegenerative disorder. Vassos et al. (pages 1347–1352) searched for clinical traits that would predict the later development of this disease. They found that people who carry the abnormality in the Huntington gene that produces HD are more hostile, particularly critical of others, than people who do not carry this risk gene even though they are otherwise healthy. These data suggest that there may be broader behavioral consequences of the HD risk gene that might be studied to provide insight into the neurobiology and prevention of this disorder.
Green Tea Treatment for Parkinson’s?
Does the consumption of green tea, widely touted to have beneficial effects on health, also protect brain cells? Guo et al. (pages 1353–1362) show that polyphenols isolated from green tea protect dopamine neurons in a rat model of Parkinson’s disease (PD). The authors show that this protective effect is mediated by inhibition of the ROS-NO pathway, a pathway that may contribute to cell death in PD. Future research will be needed to determine whether this protective effect extends to humans with PD.
Clinical Trial Findings: Drug Treatments
Marder et al. (pages 1363–1370) examined the efficacy and safety of paliperidone extended-release (ER) tablets, a new psychotropic agent for the treatment of schizophrenia, in a 6-week, randomized, placebo-controlled trial. Patients treated with paliperidone ER (6 mg and 12 mg) demonstrated significant improvement in their symptoms and a clinically relevant change in personal and social functioning. Paliperidone ER was well tolerated and may provide a new treatment option for schizophrenia.
Keller et al. (pages 1371–1379) evaluated the comparative efficacy and safety of venlafaxine ER and fluoxetine in outpatients with recurrent unipolar major depression in a multi-center, double-blind study. Nearly 80% of the patients achieved at least an adequate therapeutic response to acute phase treatment with venlafaxine ER or fluoxetine, and almost none of the responders who continued on treatment for 6 months relapsed.
Abnormalities in the Elderly Brain
After middle age, structural integrity of the “insulation” (myelin) of the “wires” (axons) of the brain begins breaking down. This process is most pronounced in later-developing brain regions and is accelerated by a gene variation that predisposes to Alzheimer’s disease (AD), apolipoprotein E 4 (ApoE4). Bartzokis et al. (pages 1380–1387) used magnetic resonance imaging (MRI) to demonstrate a specific association between cognitive speed and an MRI measure that may be related to myelin breakdown in healthy and asymptomatic “younger-old” individuals that are ApoE4 positive.
Behavioral disturbance is common in AD, but the brain mechanisms underlying these symptoms are poorly understood. Using functional MRI (fMRI), Wright et al. (pages 1388–1395) report that the amygdala, a brain region involved in emotion processing, is excessively active in AD patients when viewing both neutral and emotional faces. They also found that this increased amygdala activity correlated with the severity of irritability and agitation symptoms in the AD individuals, indicating that these functional alterations may represent a marker for specific forms of behavioral disturbances in AD.
Abnormalities in the brain white matter may occur in individuals with schizophrenia as well as with normal aging. Chang et al. (pages 1396–1404) found lower levels of N-acetyl acetate (NAA) and related compounds and elevated glutamate + glutamine and myoinositol concentrations in elderly schizophrenic subjects, especially those with declined cognitive function. These patients also showed age-related decreases of choline and creatine in the frontal white matter.
Using transcranial magnetic stimulation and electrophysiological and biochemical investigations in AD patients and in an AD animal model, Battaglia et al. (pages 1405–1412) describe a new approach for translational research in the field of synaptic plasticity and neurodegeneration that bridges data in rodents and humans. They found that both patients and mice display deficient N-methyl-D-aspartate (NMDA)-dependent synaptic plasticity, providing evidence for an impaired NMDA receptor signaling.
A Biomarker for AD is Associated with Risk for Depression in the Elderly
Low plasma levels of amyloid-β peptide 42 (Aβ42), a biomarker of AD, is associated with depressive symptoms in an elderly population without cardiovascular disease. Sun et al. (pages 1413–1417) now report that antidepressant use does not influence the relationship between depression and low plasma Aβ42. Prospective studies are needed to determine whether depression associated with low plasma Aβ42 predicts the onset of AD.
Disrupted Prepulse Inhibition May Indicate Bipolar Disorder Susceptibility
Giakoumaki et al. (pages 1418–1422) found that patients with bipolar disorder and their healthy siblings may have a deficit in the ability to “filter” sensory input, as suggested by a reduced ability to suppress the startle response to the second of two sounds. These data suggest that deficient sensory filtering may be associated with the heritable risk for bipolar disorder.
Lithium Reduces FoxO3a Transcriptional Activity
FoxO3a is a neurotrophin-regulated transcription factor that plays important roles in cell fate, differentiation, survival and stress regulation. Mao et al. (pages 1423–1430) found that lithium largely suppressed FoxO3a-induced gene expression by reducing the amount of available FoxO3a for its action. The effect of lithium does not require active neurotrophin signaling, which may help to explain the efficacy of lithium in mood disorders, where there may be deficits in neurotrophin function.
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© 2007 Published by Elsevier Inc. All rights reserved.
