RESUMO
Mouse models of food allergy have contributed to our understanding of various aspects of the disease, including susceptibilities, symptom spectra, cellular mechanisms, and therapeutic approaches. Previously, we used a mouse model of non-anaphylactic cow's milk allergy (CMA) and investigated sex- and strain-dependent differences in immunological, neurological, and behavioral sequelae. We showed that male C57BL/6J mice sensitized to a bovine whey protein, ß-lactoglobulin (BLG; Bos d 5), exhibited anxiety- and depression-like behavior upon acute allergen challenge. Systemic levels of BLG-specific immunoglobulins, cytokines and chemokines were also elevated in the sensitized mice. Furthermore, neuroinflammation and intestinal dysbiosis were evident as the possible causes of the altered behavior. To assess whether frequent allergen exposure influences CMA-associated pathologies over an extended period in this subclinical model, we placed BLG-sensitized mice on a whey protein (WP)-containing or whey-free control (CTL) diet for 3 months. As expected, allergen-specific IgE was significantly elevated in the plasma after completing the 5-week sensitization phase. However, the IgE levels declined in both diet groups after 3 months. In contrast, allergen-specific IgG1 stayed elevated in sensitized mice with the CTL diet, and the WP diet to a lesser extent. Interestingly, BLG-sensitized mice on the WP diet exhibited anxiety-like behavior and a trend toward spatial memory decline compared to the sham or the sensitized mice on the CTL diet. Moreover, increased immunoreactivities for GFAP and Iba1 and elevated levels of CXCL13 and CCL12, the chemokines involved in central leukocyte recruitment and other neurological diseases, were also observed in the brain. We demonstrated that sensitization to the whey protein, particularly with continuous allergen exposure, resulted in persistent neuroinflammation and associated behavioral changes despite lowered allergen-specific immunoglobulin levels. These results suggested that continuous consumption of the offending allergen may lead to adverse consequences in the brain even after desensitization.
RESUMO
BACKGROUND: Distinguishing between a primary psychotic disorder with concurrent substance abuse (PPD+SA) and a substance-induced psychotic disorder (SIPD) can be diagnostically challenging. We aimed to determine if these two diagnoses are clinically distinct, particularly in relation to psychopathology. In addition, we aimed to examine the specific clinical features of cannabis-induced psychotic disorder (CIPD) as compared to primary psychotic disorder with concurrent cannabis abuse (PPD+CA) and also to SIPD associated with any substance. METHODS: A systematic review of SIPD literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Using strict inclusion criteria, a total of six studies examining SIPD were included in the review (two of which only considered psychosis induced by cannabis alone). The findings did not reveal many consistent differences in psychopathology. However, we did find that that compared to PPD+SA, individuals with SIPD have a weaker family history of psychotic disorder; a greater degree of insight; fewer positive symptoms and fewer negative symptoms; more depression (only in CIPD) and more anxiety. CONCLUSION: There remains a striking paucity of information on the psychopathology, clinical characteristics and outcome of SIPD. Our review highlights the need for further research in this area.
