Mecp2 deletion results in profound alterations of developmental and adult functional connectivity.

As a regressive neurodevelopmental disorder with a well-established genetic cause, Rett syndrome and its Mecp2 loss-of-function mouse model provide an excellent opportunity to define potentially translatable functional signatures of disease progression, as well as offer insight into the role of Mecp2 in functional circuit development. Thus, we applied widefield optical fluorescence imaging to assess mesoscale calcium functional connectivity (FC) in the Mecp2 cortex both at postnatal day (P)35 in development and during the disease-related decline. We found that FC between numerous cortical regions was disrupted in Mecp2 mutant males both in juvenile development and early adulthood. Female Mecp2 mice displayed an increase in homotopic contralateral FC in the motor cortex at P35 but not in adulthood, where instead more posterior parietal regions were implicated. An increase in the amplitude of connection strength, both with more positive correlations and more negative anticorrelations, was observed across the male cortex in numerous functional regions. Widespread rescue of MeCP2 protein in GABAergic neurons rescued none of these functional deficits, nor, surprisingly, the expected male lifespan. Altogether, the female results identify early signs of disease progression, while the results in males indicate MeCP2 protein is required for typical FC in the brain.

United States Department of Justice findings letters in psychiatric hospital CRIPA cases: an aid or a distraction?

The Civil Rights of Institutionalized Persons Act (CRIPA) of 1980 allows the United States Department of Justice (DOJ) to investigate and file lawsuits against certain institutions, including state and county psychiatric hospitals, where individuals within may face unconstitutional conditions. Subsequent to an investigation and before negotiations or litigation, the state is provided a Findings Letter generated by the DOJ that generally contains recommended remedial measures. It has never been determined to what extent a Findings Letter provides a state with a recommendation specific to the institution for corrective action before the state enters into negotiations with the DOJ. Three study groups were derived from a sample of 15 Findings Letters written to states concerning their psychiatric hospitals between 2003 and 2009. The individual recommended remedial measures, labeled texts of interest (TOI), were identified, and the degree of overlap among the Findings Letters was determined. To a surprising degree, TOIs overlapped to various extents, from exact copies of text to paraphrased versions, in Findings Letters written between 2003 and 2009 to different states and for multiple state hospitals in the same state. The recommended remedial measures provided in the DOJ's Findings Letters are not specific to each state hospital's deficiencies. The Findings Letters offer limited guidance to the state on how to remedy the deficiencies before negotiating with the DOJ. This lack of specificity causes inefficient and delayed remediation of unconstitutional conditions and other deficiencies in care and treatment in psychiatric hospitals. While the current process most often leads to improvements in state hospitals, it is a costly, inefficient remedy, despite the possibility of alternative remedial processes of less expensive and equal or greater effectiveness.

Pretreatment regional brain glucose uptake in the midbrain on PET may predict remission from a major depressive episode after three months of treatment.

In order to test the hypotheses that pretreatment metabolic activity in the midbrain and the rostral anterior cingulate may predict remission in response to medications enhancing monoaminergic transmission, we compared relative regional cerebral metabolic rate of glucose (rCMRglu) using positron emission tomography (PET) in medication-free patients with major depression who remitted after 3 months of monoaminergic medication, with non-remitters on the same treatment. [(18)F]-FDG PET was conducted in a group of 33 drug-free DSM-IV major depression subjects prior to antidepressant treatment. Patients were prescribed paroxetine initially (61%) unless they had failed paroxetine previously. Treatment was then managed by the subjects' own physician with 91% receiving a selective serotonin reuptake inhibitor and 78% another non-selective monoamine reuptake inhibitor during the 3 months of treatment. Voxel-based parametric brain maps of remitters were compared with maps of non-remitters using SPM2. Remission was defined as a >50% decrease in and a final score of