Aggression and trauma experiences among carer-relatives of people with psychosis

Exposure to aggression and associated psychological outcomes are poorly characterised among carer-relatives of people with psychosis. Carer-relatives (N = 106) completed questionnaires assessing socio-demographics and perceived prevalence of aggression in their caring role in the last 12 months. Carers exposed to moderate–severe levels of aggression were re-approached to assess PTSD and coping strategies. Most respondents (77.4%) reported experiencing moderate–severe levels of aggression. Increased contact with (M = 15.12 vs. M = 6.71 days per month), and significantly higher ratings of affective, antisocial, negative and psychotic symptomology in affected relatives were associated with experiences of moderate–severe aggression. Approximately half of the moderate–severe respondents reported potentially significant levels of PTSD (52%, N = 34), which was associated with greater exposure to verbal aggression and increased usage of coping strategies. Comparable ratios of physical to non-physical aggression to those reported by professional carers working in acute psychiatric treatment settings were reported. Carer-relatives require greater levels of information and support to assist them in their community caring roles

N-Desmethylclozapine, a major clozapine metabolite, acts as a selective and effecacious delta-opioid agonist at recombinant and native receptors

The present study examined the effects of N-desmethylclozapine (NDMC), a biologically active metabolite of the atypical antipsychotic clozapine, at cloned human opioid receptors stably expressed in Chinese hamster ovary (CHO) cells and at native opioid receptors present in NG108-15 cells and rat brain. In CHO cells expressing the delta-opioid receptor (CHO/DOR), NDMC behaved as a full agonist both in stimulating [(35)S]GTPgammaS binding (pEC(50)=7.24) and in inhibiting cyclic AMP formation (pEC(50)=6.40). NDMC inhibited [(3)H]naltrindole binding to CHO/DOR membranes with competition curves that were modulated by guanine nucleotides in an agonist-like manner. Determination of intrinsic efficacies by taking into consideration both the maximal [(35)S]GTPgammaS binding stimulation and the extent of receptor occupancy at which half-maximal effect occurred indicated that NDMC had an efficacy value equal to 82% of that of the full delta-opioid receptor agonist DPDPE, whereas clozapine and the other clozapine metabolite clozapine N-oxide displayed much lower levels of agonist efficacy. NDMC exhibited poor agonist activity and lower affinity at the kappa-opioid receptor and was inactive at mu-opioid and NOP receptors. In NG108-15 cells, NDMC inhibited cyclic AMP formation and stimulated the phosphorylation of extracellular signal-regulated kinase 1/2 by activating the endogenously expressed delta-opioid receptor. Moreover, in membranes of different brain regions, NDMC stimulated [(35)S]GTPgammaS binding and regulated adenylyl cyclase activity and the effects were potently antagonized by naltrindole. These data demonstrate for the first time that NDMC acts as a selective and efficacious delta-opioid receptor agonist and suggest that this unique property may contribute, at least in part, to the clinical actions of the atypical antipsychotic clozapine