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Atypical antipsychotics bind to multiple receptor types and subtypes. Improved outcomes in schizophrenia are linked to activity at D2 and serotonin receptors 5-HT7, 5-HT2A and 5-HT1A.
To characterize the receptor-binding profile of lurasidone and other antipsychotics.
To compare receptor-binding profiles of antipsychotics.
Replicated, side-by-side receptor-binding assays used human recombinant receptors (for 5-HT7, α2A, and α2C) or membrane-fractions of animal CNS tissue. Affinities were determined via Hill plot analysis for IC50values; Ki values were determined using Ki=IC50/(1+ S/Kd) (S=concentration of competing radioligand, Kd=dissociation constant).
Lurasidone displayed potent binding and full antagonism at dopamine D2(Ki, 1.68nM) and serotonin 5-HT2A(Ki, 2.03nM) receptors (the highest D2affinity of all tested agents). Lurasidone's dopamine binding was selective for D2receptors. Unlike other antipsychotics tested, lurasidone had very high affinity and full antagonism at serotonin 5-HT7(Ki, 0.49nM), and nanomolar affinity (Ki=6.75nM) with weak-moderate partial agonism at serotonin 5-HT1Areceptors., Lurasidone showed higher affinity for 5-HT7, 5-HT2A, and 5-HT1Areceptors relative to D2receptor-binding than other agents. Lurasidone displayed moderate affinity for α2C adrenoceptors (Ki, 10.8nM); moderate-weak affinity for α1adrenoceptors (Ki, 48nM); and minimal or unappreciable affinity for receptors associated with undesirable effects (5-HT2C [Ki, 415nM], histamine H1[IC50>1000nM] and muscarinic [cholinergic] M1[IC50>1000nM] receptors).
The unique pharmacological profile of lurasidone is consistent with observed antipsychotic efficacy, low-tomoderate likelihood of EPS, low weight-gain potential, and possible mood, anxiety, and cognitive benefits.
Schizophrenia is characterized by poor social interaction contributing to poor functional outcome. Particularly nonverbal communication is disturbed. Neural correlates of impaired gesturing are currently unclear. We thus tested functional correlates of gesturing in schizophrenia patients and healthy controls.
We tested 22 patients and 25 controls with an event-related fMRI (instructed delay) paradigm to dissociate brain activation during planning and execution of meaningful (e.g. use scissors) and meaningless novel gestures. Preprocessing included realignment, coregistration, normalization and spatial smoothing. We used a two stage mixed effects model for statistical analysis. Conditions were contrasted against a linguistic control within and between groups. We correlated psychopathological characteristics with beta estimates of brain areas with between group effects.
During planning and execution of both gesture subtypes both groups activated brain areas of the ventral and dorsal stream. However patients’ activity was less prominent and more left lateralized. During planning patients showed additional activity in bilateral temporal poles, amygdala and hippocampus associated with the level of delusions. Furthermore patients had increased dorsomedial prefrontal cortex and precuneus activity when planning meaningless gestures.
During the planning of meaningless gestures we detected aberrant activation of limbic structures in patients typically implicated in delusion formation, which also correlated with current severity of delusions. Moreover, planning of meaningless gestures relied on areas relevant for strategic control and attention. These results argue for a pathologic search for meaning in neutral gestures and increased control effort during planning of meaningless gestures in schizophrenia.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Depressive symptoms are highly prevalent in nursing home (NH) residents. The relationship between depressive symptoms and everyday competence in terms of basic (BaCo) and expanded everyday competence (ExCo; see Baltes et al., 2001) in the NH setting is, however, not clear. Applying Lewinsohn's depression model, we examined how residents’ BaCo and ExCo relate to their depressive symptoms. Furthermore, we investigated the mediating role of perceived control.
Cross-sectional data from 196 residents (Mage = 83.7 years, SD = 9.4 years) of two German NHs were analyzed. Study variables were assessed by the Geriatric Depression Scale-Residential (GDS-12R), maximal gait speed (BaCo), proxy ratings of residents’ in-home activity participation, and self-initiated social contact done by staff (ExCo). Structural equation modeling (SEM) was used and a simulation study was included to determine power and potential estimation bias.
At the descriptive level, one quarter of the residents showed symptoms of depression according to the GDS-12R cut-off criterion. Residents’ BaCo and ExCo were independently and equally strongly associated with their depressive symptoms in the SEM analysis. These findings were affected neither by cognitive impairment, sex, nor age. Perceived control mediated between BaCo but not ExCo and depressive symptoms.
Future research needs to follow the connection between residents’ everyday competence and their depressive symptoms longitudinally to better understand the underlying mechanisms.
Childhood maltreatment (CM) has consistently been linked with adverse outcomes including substance use disorders and adult sexual revictimization. Adult sexual victimization itself has been linked with psychopathology but has predominately been studied in women. The current investigation examines the impact of CM and co-occurring psychopathology on adult sexual victimization in men and women, replicating findings in three distinct samples.
We investigated the association between continuous CM factor scores and adult sexual victimization in the Childhood Trauma Study (CTS) sample (N = 2564). We also examined the unique relationship between childhood sexual abuse (CSA) and adult sexual victimization while adjusting for co-occurring substance dependence and psychopathology. We replicated these analyses in two additional samples: the Comorbidity and Trauma Study (CATS; N = 1981) and the Australian Twin-Family Study of Alcohol Use Disorders (OZ-ALC; N = 1537).
Analyses revealed a significant association with CM factor scores and adult sexual victimization for both men and women across all three samples. The CSA factor score was strongly associated with adult sexual victimization after adjusting for substance dependence and psychopathology; higher odds ratios were observed in men (than women) consistently across the three samples.
A continuous measure of CSA is independently associated with adult sexual trauma risk across samples in models that included commonly associated substance dependence and psychopathology as covariates. The strength of the association between this CSA measure and adult sexual victimization is higher in magnitude for men than women, pointing to the need for further investigation of sexual victimization in male community samples.
Thoroughly revised, and fully updated for DSM-5, the new edition of this practice-focused book guides clinical psychology trainees through a field which is rapidly evolving. Through real-world exploration of the scientist-practitioner model, the book helps readers to develop the core competencies required in an increasingly interdisciplinary healthcare environment. New chapters cover brief interventions, routine monitoring of treatment progress, and managing alliance ruptures. Practical skills such as interviewing, diagnosis, assessment, treatment and case management are discussed with emphasis on the question 'how would a scientist-practitioner think and act?' By demonstrating how an evidence-base can influence every decision that a clinical psychologist makes, the book equips trainees to deliver the accountable, efficient, effective client-centred service which is demanded of professionals in the modern integrated care setting. Essential reading for all those enrolled in, or contemplating, postgraduate studies in clinical psychology.