Patients with paraneoplastic cerebellar degeneration (PCD) offer the opportunity to explore the mechanisms underlying tumor immunity and immune-mediated neuronal degeneration. Cytotoxic T lymphocytes (CTLs) specific for the PCD onconeural antigen cdr2 found in the blood of patients with PCD are likely to be effectors of PCD tumor immunity. Here, we suggest a role for CTLs in the autoimmune destruction of Purkinje neurons. More than 75% of the cells obtained from the cerebrospinal fluid (CSF) of PCD patients were CD3+ alphabeta T cells. In patients with active/progressive disease, 20% to 40% of CSF cells were activated T cells, and the CD4+ helper cells were Th1-type cells. Three PCD patients were given tacrolimus, a specific inhibitor of activated T cells, which markedly reduced these cells in the CSF. Tacrolimus also reduced the number of activated cdr2-specific CTLs in the peripheral blood, but did not lead to tumor recurrence. We suggest that activated cdr2-specific CTLs in the CSF contribute to Purkinje degeneration in PCD, and that tacrolimus therapy may benefit patients with paraneoplastic neurological disease and other T cell-mediated autoimmune neurological disorders.

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Abstract. In autism and technology research, technologies are often developed by researchers targeting specific social and communication difficulties experienced by individuals with autism. In some technologybased projects, children and adults with autism as well as parents, carers, teachers, and other professionals, are involved as users, informers, and (more rarely) as co-designers. However, much less is known about the views of the autism community about the needs they identify as areas that could be addressed through innovative technological solutions. This paper describes the ASCmeI.T. project which encourages members of the autism community to download a free app to answer the question: If there was one new technology to help people with autism, what would it be? This project provides a model of e-participation in which people from the autism community are involved from the start so that new developments in digital technologies can be better matched to support the needs of users.

Objective Owing to the clinical relationship between bipolar disorder and nicotine dependence, we investigated two research questions: (i) are genetic associations with nicotine dependence different in individuals with bipolar disorder as compared with individuals without bipolar disorder, and (ii) do loci earlier associated with nicotine dependence have pleiotropic effects on these two diseases. Method Our study consisted of 916 cases with bipolar disorder and 1028 controls. On the basis of known associations with nicotine dependence, we genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three bins) in the regions of CHRNA5 and CHRNA3. Results To determine whether the genetic associations with nicotine dependence are different in bipolar disorder than in the general population, we compared allele frequencies of candidate SNPs between individuals with nicotine dependence only and individuals with both nicotine dependence and bipolar disorder. There were no statistical differences between these frequencies, indicating that genetic association with nicotine dependence is similar in individuals with bipolar disorder as in the general population. In the investigation of pleiotropic effects of these SNPs on bipolar disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953, were significantly associated with bipolar disorder (odds ratio 1.7, 95% confidence interval: 1.2–2.4, P = 0.001). This association remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. Conclusion Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder. Psychiatr Genet 00:000–000.

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