No abstract

An association between longer DUP and accelerated hippocampal atrophy during initial treatment suggests that psychosis may have persistent, possibly deleterious, effects on brain structure. Additional studies are needed to replicate these exploratory findings of molecular mechanisms by which untreated psychosis may affect hippocampal volume and to determine whether these effects account for the known association between longer DUP and poor outcome.

Background Converging evidence implicates the anterior hippocampus in the proximal pathophysiology of schizophrenia. Although resting state functional connectivity (FC) holds promise for characterizing anterior hippocampal circuit abnormalities and their relationship to treatment response, this technique has not yet been used in first-episode psychosis (FEP) patients in a manner that distinguishes the anterior from posterior hippocampus. Methods We used masked-hippocampal-group-independent component analysis with dual regression to contrast subregional hippocampal–whole brain FC between healthy controls (HCs) and antipsychotic naïve FEP patients (N = 61, 36 female). In a subsample of FEP patients (N = 27, 15 female), we repeated this analysis following 8 weeks of second-generation antipsychotic treatment and explored whether baseline FC predicted treatment response using random forest. Results Relative to HC, untreated FEP subjects displayed reproducibly lower FC between the left anteromedial hippocampus and cortical regions including the anterior cingulate and insular cortex (P < .05, corrected). Anteromedial hippocampal FC increased in FEP patients following treatment (P < .005), and no longer differed from HC. Random forest analysis showed baseline anteromedial hippocampal FC with four brain regions, namely the insular–opercular cortex, superior frontal gyrus, precentral gyrus, and postcentral gyrus predicted treatment response (area under the curve = 0.95). Conclusions Antipsychotic naïve FEP is associated with lower FC between the anterior hippocampus and cortical regions previously implicated in schizophrenia. Preliminary analysis suggests that random forest models based on hippocampal FC may predict treatment response in FEP patients, and hence could be a useful biomarker for treatment development.

The molecular aetiology of steroid-induced osteonecrosis (ON) is unclear. The aim of this study was to investigate changes in the femoral head blood supply and vascular endothelial growth factor (VEGF) protein levels following steroid-induced ON of rabbit femoral heads in the early stage of the disease, and to investigate a possible mechanism for ON. Using a classic protocol, ON was induced in 30 male 28-week old New Zealand white rabbits. An additional 15 untreated rabbits served as controls. Change of blood supply in the proximal femur was assessed by dynamic magnetic resonance imaging and microangiography. The VEGF protein and mRNA levels were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction, respectively. After 6 weeks, the results indicated that VEGF protein and mRNA levels were significantly lower and femoral head blood supply had also decreased significantly in ON(+) rabbits compared with controls. The down-regulation of VEGF may play a critical role in the disease process of ON.