NRXN1 is associated with enlargement of the temporal horns of the lateral ventricles in psychosis.

Schizophrenia, Schizoaffective, and Bipolar disorders share behavioral and phenomenological traits, intermediate phenotypes, and some associated genetic loci with pleiotropic effects. Volumetric abnormalities in brain structures are among the intermediate phenotypes consistently reported associated with these disorders. In order to examine the genetic underpinnings of these structural brain modifications, we performed genome-wide association analyses (GWAS) on 60 quantitative structural brain MRI phenotypes in a sample of 777 subjects (483 cases and 294 controls pooled together). Genotyping was performed with the Illumina PsychChip microarray, followed by imputation to the 1000 genomes multiethnic reference panel. Enlargement of the Temporal Horns of Lateral Ventricles (THLV) is associated with an intronic SNP of the gene NRXN1 (rs12467877, P = 6.76E-10), which accounts for 4.5% of the variance in size. Enlarged THLV is associated with psychosis in this sample, and with reduction of the hippocampus and enlargement of the choroid plexus and caudate. Eight other suggestively significant associations (P < 5.5E-8) were identified with THLV and 5 other brain structures. Although rare deletions of NRXN1 have been previously associated with psychosis, this is the first report of a common SNP variant of NRXN1 associated with enlargement of the THLV in psychosis.

Catatonia Associated With Systemic Lupus Erythematosus (SLE): A Report of Two Cases and a Review of the Literature.

BACKGROUND: Systemic lupus erythematosus (SLE) is known to cause neuropsychiatric symptoms (NPSLE). While not formally recognized as a syndrome associated with NPSLE, catatonia has frequently been reported. OBJECTIVE: It is important for clinicians to recognize and treat catatonia as a potential manifestation of NPSLE. We present 2 cases of SLE with catatonia and review the cases reported in the literature. METHODS: We performed a PubMed search for reported cases of catatonia in SLE. Case reports that met Diagnostic and Statistical Manual of Mental Disorders-5th ed. diagnostic criteria for catatonia were summarized to assess common diagnostic tests and treatments. RESULTS: Twenty-six articles describing a total of 35 patients (all female), in addition to our 2 patients, were included in the report. All but one of the patients received immunosuppressive therapy for treatment of SLE. To treat catatonia symptoms, 81% of the patients received benzodiazepines, and 38% received electroconvulsive therapy. CONCLUSIONS: Catatonia can be a manifestation of NPSLE, particularly in the presence of serologies and symptoms indicative of an active lupus flare. Management of catatonia involves management of the underlying condition, in this case immunomodulatory treatments for NPSLE; avoidance of treatments, such as antipsychotics, which can worsen catatonia; and symptomatic treatments for catatonia, for which benzodiazepines are a first-line treatment, and electroconvulsive therapy when catatonia is refractory to benzodiazepines.

Establishment of atypical-teratoid/rhabdoid tumor (AT/RT) cell cultures from disseminated CSF cells: a model to elucidate biology and potential targeted therapeutics.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm that usually affects infants and young children. In this report, we describe culture conditions that enabled the sustained growth of tumor cells obtained from the cerebrospinal fluid (CSF) of an infant with AT/RT. These cells retained the morphological and biomarker characteristics of the original tumor. A screening of receptor tyrosine kinases identified the presence of phosphorylated ErbB4, Insulin-R, PDGFR and IGF-IR, which appear to depend on Hsp90 to maintain their active form. IGF-IR activity is consistent with data from other established AT/RT cell lines. Inhibition of IGF-IR by the small molecular weight inhibitor AEW541 led to growth suppression of cultured AT/RT cells. In addition, neutralizing antibodies to IGF-II also inhibited the growth of these cells suggesting a potential autocrine function for this cytokine. We also compared cultured AT/RT cells to established cell lines to identify consistent drug sensitivity patterns among these cells. In addition to previously described cell lines and xenograft models, continuous culture of CSF derived cells may also provide an effective way to study the biology of AT/RT and to identify potential targets for future therapeutics for this tumor.