To support the role of DISC1 in human psychiatric disorders, we identified and analyzed two independently derived ENU-induced mutations in Exon 2 of mouse Disc1. Mice with mutation Q31L showed depressive-like behavior with deficits in the forced swim test and other measures that were reversed by the antidepressant bupropion, but not by rolipram, a phosphodiesterase-4 (PDE4) inhibitor. In contrast, L100P mutant mice exhibited schizophrenic-like behavior, with profound deficits in prepulse inhibition and latent inhibition that were reversed by antipsychotic treatment. Both mutant DISC1 proteins exhibited reduced binding to the known DISC1 binding partner PDE4B. Q31L mutants had lower PDE4B activity, consistent with their resistance to rolipram, suggesting decreased PDE4 activity as a contributory factor in depression. This study demonstrates that Disc1 missense mutations in mice give rise to phenotypes related to depression and schizophrenia, thus supporting the role of DISC1 in major mental illness.

Dual-modality imaging with HRCT and MR of petrous bone and MR brain in the precochlear implant pediatric population detects abnormalities related to deafness, which would not otherwise be found using either modality alone. There is overlap between the imaging modalities in the type of abnormalities detected, and we present a case for selective use of HRCT within a diagnostic algorithm, using the patient risk factors we have identified.

Objectives To describes a cadaveric temporal bone model of labyrinthitis ossificans and investigate the utility of intra-operative C-arm computed tomography (CBCT) in facilitating cochlear implantation. Design Cadaveric temporal bone study. Methods Five cadaveric heads had cement introduced into the 10 cochleas. CBCT and a conventional CT scans were compared to asses the extent of cochlear obliteration. The cement was drilled-out (under CBCT guidance, if required) and a cochlear implant electrode arrays (from 3 different manufacturers) inserted. Results CBCT images demonstrated temporal bone anatomy and the extent of cochlear obliteration as clearly as conventional CT in all cases. Intra-operative CBCT guided drilling and facilitated electrode placement in 2 out of 5 heads (3/10 ears). Streak-artifact from the electrodes of two devices partially obscured image clarity. Conclusions The obliterated cochlear model reproduced a disease-ossified cochlear both radiographically and surgically. CBCT is useful for intra-operative imaging, to facilitate electrode array placement in the obliterated or congenitally abnormal cochlea.

Endoscopic image capture may provide a clear objective record of TM retraction, but current staging systems have unsatisfactory reliability when applied to such images, and retraction stage correlates poorly with hearing threshold. Modification of retraction assessment to improve validity and clinical relevance is proposed.