ABSTRACT
UNLABELLED: OBJECTIVE/INTRODUCTION: Lurasidone is an atypical antipsychotic medication approved for the treatment of schizophrenia over a dose range of 40-160 mg/day. This study examined D2 receptor occupancy and its association with clinical improvement and side effects in patients with schizophrenia or schizoaffective disorder following repeated doses of 80, 120, or 160 mg/day of lurasidone. METHODS: Twenty-five patients with The Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnoses of schizophrenia or schizoaffective disorder were washed out of their antipsychotic medications (5 half-lives) and randomly assigned to 80, 120, or 160 mg/day of lurasidone. Subjects were imaged with 18F-fallypride at baseline and at steady-state lurasidone treatment to determine D2 receptor occupancy. RESULTS: Blood lurasidone concentration (plus major metabolite), but not dose, significantly correlated with D2 receptor occupancy. D2 receptor occupancy in several subcortical structures is associated with positive but not negative symptom improvement or the presence of movement symptoms. DISCUSSION: Blood concentrations greater than 70 ng/mL may be required to achieve a 65% occupancy level in subcortical areas. Intersubject blood concentrations at fixed dose were highly variable and may account for the lack of dose correlations. CONCLUSIONS: Positron emission tomography (PET) occupancy data suggest that greater than 65% occupancy can be achieved across the dose range of 80-160 mg/day and that some patients require higher doses to achieve antipsychotic efficacy; this finding supports prior randomized clinical trial results.
Subject(s)
Antipsychotic Agents/therapeutic use , Isoindoles/therapeutic use , Psychotic Disorders/drug therapy , Receptors, Dopamine D2/metabolism , Schizophrenia/drug therapy , Thiazoles/therapeutic use , Adult , Algorithms , Benzamides/pharmacokinetics , Brain/diagnostic imaging , Brain/drug effects , Dose-Response Relationship, Drug , Female , Humans , Lurasidone Hydrochloride , Male , Middle Aged , Positron-Emission Tomography , Psychiatric Status Rating Scales , Psychotic Disorders/diagnostic imaging , Pyrrolidines/pharmacokinetics , Schizophrenia/diagnostic imaging , Statistics as Topic , Young AdultABSTRACT
The extent to which the brain regions associated with face processing are selective for that specific function remains controversial. In addition, little is known regarding the extent to which face-responsive brain regions are selective for human faces. To study regional selectivity of face processing, we used functional magnetic resonance imaging to examine whole brain activation in response to human faces, dog faces, and houses. Fourteen healthy right-handed volunteers participated in a passive viewing, blocked experiment. Results indicate that the lateral fusiform gyrus (Brodmann's area 37) responds maximally to both dog and human faces when compared with other sites, followed by the middle/inferior occipital gyrus (BA 18/19). Sites that were activated by houses versus dog and human faces included the medial fusiform gyrus (BA 19/37), the posterior cingulate (BA 30), and the superior occipital gyrus (BA 19). The only site that displayed significant differences in activation between dog and human faces was the lingual/medial fusiform gyrus. In this site, houses elicited the strongest activation, followed by dog faces, while the response to human faces was negligible and did not differ from fixation. The parahippocampal gyrus/amygdala was the sole site that displayed significant activation to human faces, but not to dog faces or houses.
