MRI and neuropsychological improvement in Huntington disease following ethyl-EPA treatment.

A 6-month randomized, placebo-controlled pilot study of the ethyl-ester of eicosapentaenoic acid (ethyl-EPA) was carried out in seven in-patients with advanced (stage III) Huntington's disease (three on ethyl-EPA, four on placebo; no significant difference in age or sex between the groups). After 6 months all the patients treated with ethyl-EPA improved on the orofacial component of the Unified Huntington's Disease Rating Scale while all the patients on placebo deteriorated on this scale (p < 0.03). Following subvoxel registration of follow-up 3D MRI brain scans with baseline scans, subtraction images showed that while the placebo was associated with progressive cerebral atrophy, the ethyl-EPA was associated with a reverse process. We conclude that treatment with ethyl-EPA is associated with beneficial motor and MRI changes.

Essential fatty acids in Huntington's disease.

Huntington's disease is an inherited neurodegenerative disorder due to a mutation in exon 1 of the Huntingtin gene that encodes a stretch of polyglutamine (polyQ) residues close to the N-terminus of the huntingtin protein. Aggregated polyQ residues are highly toxic to the neuronal cells when they enter the cell nucleus. The mechanisms by which aggregated polyQ induces neurodegeneration include the binding of abnormal huntingtin to cyclic adenosine monophosphate response element binding protein, which hampers its ability to turn on transcription of other genes; mutant huntingtin binding to the active site on the cyclic adenosine monophosphate response element binding protein, which is essential for its acetyltransferase activity and, hence, the drugs that inhibit histone deacetylase arrest polyQ-dependent neurodegeneration; and/or disrupting the ubiquitin-proteasome system. Transgenic R6/1 mice that incorporate a human genomic fragment containing promoter elements exon 1 and a portion of intron 2 of the huntingtin gene responsible for Huntington's disease develop late-onset neurologic deficits in a manner similar to the motor abnormalities of Huntington's disease and show increased survival rates and decreased neurologic deficits when supplemented with essential fatty acids throughout life. A randomized, placebo-controlled, double-blind study has shown that highly unsaturated fatty acids are beneficial to patients with Huntington's disease. These results raise the possibility that unsaturated fatty acids may prevent or arrest polyQ aggregation, inhibit histone deacetylase, and/or activate the ubiquitin-proteasome system. In view of the encouraging results with essential fatty acids in Huntington's disease, it is proposed that their possible use in other neurodegenerative conditions need to be explored.

Abuse of carers by relatives with severe mental illness.

BACKGROUND: Relatives often experience considerable problems looking after a family member with severe mental illness. The problems arising from verbal and physical abuse are not well researched or acknowledged. AIMS: To examine the frequency with which family carers experienced verbal and physical abuse from relatives who were being looked after by a community mental health service and to identify the correlates and consequences of that abuse. METHOD: Interviews with all the clients of a community mental health service in suburban Melbourne who had regular contact with a family carer together with interviews with the carers. RESULTS: One hundred and one clients and their family carers were interviewed. Supporting a previous study of patients on an acute admission ward, the experiences of verbal and physical abuse were positively correlated. Higher rates of abuse were associated with poor relationships between patients and their families and a history of poly-drug misuse and previous criminal offences on the part of the patient. Relatives experiencing higher levels of abuse were more likely to have. symptoms of emotional distress and were rated as experiencing more burden. CONCLUSIONS: Verbal and physical abuse are not infrequent problems facing family members caring for a relative with severe mental illness. Some of the risk factors for such abuse can be identified. Care plans for family carers could usefully target risk reduction strategies to minimise the occurrence of abuse.

Transfer of risperidone and 9-hydroxyrisperidone into human milk.

OBJECTIVE: To quantify the transfer of risperidone and its active metabolite 9-hydroxyrisperidone into breast milk, estimate the amount the infant receives, measure infant plasma concentrations, and clinically assess the safety of breast feeding during maternal risperidone administration. case summaries: The transfer of risperidone and 9-hydroxyrisperidone into milk was studied in 2 breast-feeding women and one woman with risperidone-induced galactorrhea. Plasma samples were available from 2 of the women and from both breast-fed infants. The milk/plasma concentration ratio determined in 2 women was <0.5 for both compounds. The calculated relative infant "doses" were 2.3%, 2.8%, and 4.7% (as risperidone equivalents) of the maternal weight-adjusted doses. Risperidone and 9-hydroxyrisperidone were not detected in the plasma of the 2 breast-fed infants studied, and no adverse effects were noted. DISCUSSION: Risperidone therapy is sometimes necessary in breast-feeding women, raising the issue of safety in the exposed infants. Our study shows that the relative infant dose is lower than the arbitrary 10% level of concern. The data provide clear guidance on infant exposure for the cases presented. CONCLUSIONS: Maternal risperidone therapy is unlikely to be a significant hazard for the breast-fed infant in the short term. Nevertheless, decisions on whether a woman may breast-feed should be made as an individual risk-benefit analysis.