Despite the fact that a high proportion of elderly stroke patients develop mood disorders, the mechanisms underlying late-onset neuropsychiatric and neurocognitive symptoms have so far received little attention in the field of neurobiology. In rodents, aged animals display depressive symptoms following stroke, whereas young animals recover fairly well. This finding has prompted us to investigate the expression of serotonin receptors 2A and 2B, which are directly linked to depression, in the brains of aged and young rats following stroke. Although the development of the infarct was more rapid in aged rats in the first 3 days after stroke, by day 14 the cortical infarcts were similar in size in both age groups i.e. 45% of total cortical volume in young rats and 55.7% in aged rats. We also found that the expression of serotonin receptor type B mRNA was markedly increased in the perilesional area of aged rats as compared to the younger counterparts. Furthermore, histologically, HTR2B protein expression in degenerating neurons was closely associated with activated microglia both in aged rats and human subjects. Treatment with fluoxetine attenuated the expression of Htr2B mRNA, stimulated post-stroke neurogenesis in the subventricular zone and was associated with an improved anhedonic behavior and an increased activity in the forced swim test in aged animals. We hypothesize that HTR2B expression in the infarcted territory may render degenerating neurons susceptible to attack by activated microglia and thus aggravate the consequences of stroke.

Objective:To explore tolerability, safety and treatment response of flexible doses of oral paliperidone ER in patients with schizophrenia suffering from an acute episode.Methods:Interim analysis of a 6-week prospective, open-label, international study. Endpoints were the rate of responders defined as a ≥30% improvement in the Positive and Negative Syndrome Scale (PANSS) from baseline to endpoint, the Clinical Global Impression-Severity Scale (CGI-S), weight change and adverse events (AEs).Results:100 patients were analyzed (51% male, mean age 39.0±11.6 years). 82% of patients completed the study. Most frequent reasons for early discontinuation were subject choice (10%) and lack of efficacy (7%). the mean dose of paliperidone ER was 5.9 mg/day at baseline and 7.9 mg/day at endpoint. an improvement of ≥30% in total PANSS was observed in 68% of patients (95% confidence interval [CI]58%;77%], with a decrease in mean total PANSS scores from 98.2±16.2 at baseline to 71.1±20.3 at endpoint (mean change -27.1±19.9; 95%CI -31.1;-23.2, p< 0.0001) and onset of efficacy as of day 2. the percentage of patients rated as at least markedly ill in CGI-S decreased from 69% to 20.3%. AEs reported in ≥5% were insomnia (14%), tachycardia (10%), akathisia (6%), extrapyramidal disorder (6%), headache (5%) and schizophrenia (5%). Median weight gain was 0.7 kg (95% CI 0.19;1.96) from baseline to endpoint.Conclusion:This analysis supports data from recent controlled studies that flexibly dosed paliperidone ER is safe, well tolerated and associated with a clinically meaningful treatment response in patients with an acute schizophrenic episode.