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Background: Presently, there is limited guidance on the maximal dosing of psychosis drugs that is based on effectiveness rather than safety or toxicity. Current maximum dosing recommendations may far exceed the necessary degree of dopamine D2 receptor blockade required to treat psychosis. This may lead to excess harm through cognitive impairment and side effects. Aims: This analysis aimed to establish guidance for prescribers by optimally dosing drugs for psychosis based on efficacy and benefit. Methods: We used data from two dose–response meta-analyses and reviewed seven of the most prescribed drugs for psychosis in the UK. Where data were not available, we used appropriate comparison techniques based on D2 receptor occupancy to extrapolate our recommendations. Results: We found that the likely threshold dose for achieving remission of psychotic symptoms was often significantly below the currently licensed dose for these drugs. We therefore recommend that clinicians are cautious about exceeding our recommended doses. Individual factors, however, should be accounted for. We outline potentially relevant factors including age, ethnicity, sex, smoking status and pharmacogenetics. Additionally, we recommend therapeutic drug monitoring as a tool to determine individual pharmacokinetic variation. Conclusions: In summary, we propose a new set of maximum target doses for psychosis drugs based on efficacy. Further research through randomised controlled trials should be undertaken to evaluate the effect of reducing doses from current licensing maximums or from doses that are above our recommendations. However, dose reductions should be implemented in a manner that accounts for and reduces the effects of drug withdrawal. [ABSTRACT FROM AUTHOR]

The study explored the extent to which a sample of clinical psychologists in Early Intervention Psychosis (EIP) services routinely investigated trauma with clients. A novel vignette-semi-structured telephone interview approach was used. To avoid limiting conceptualisations of these phenomena, for example, by solely considering trauma as a contributory or aetiological factor in psychosis, the study was designed to allow wider exploration of relationships and other key factors. The majority of the sample reported routine investigation of severe adversity, abuse, or trauma (AAT) with clients, assuming broad definitions. Assessment procedures were collaborative and client-led. An appropriate context was deemed necessary before trauma was explored, including engagement and a psychologically safe environment. The overall findings highlighted explicit investigation of, broadly defined, trauma-related issues within heterogeneous approaches to working with psychosis. While trauma was one key factor, links with psychosis were complex in practice. Participants appeared to operate within a more complex understanding of psychosis than researchers may sometimes be willing to promote. [ABSTRACT FROM AUTHOR]

Background: Psychotic experiences and negative symptoms (PENS) are common in non-clinical populations. PENS are associated with adverse outcomes, particularly when they persist. Little is known about the trajectories of PENS dimensions in young people, nor about the precursory factors associated with these trajectories. Methods: We conducted growth mixture modelling of paranoia, hallucinations, and negative symptoms across ages 16, 17, and 22 in a community sample (N = 12 049–12 652). We then described the emergent trajectory classes through their associations with genome-wide polygenic scores (GPS) for psychiatric and educational phenotypes, and earlier childhood characteristics. Results: Three trajectory classes emerged for paranoia, two for hallucinations, and two for negative symptoms. Across PENS, GPS for clinical help-seeking, major depressive disorder, and attention deficit hyperactivity disorder were associated with increased odds of being in the most elevated trajectory class (OR 1.07–1.23). Lower education GPS was associated with the most elevated trajectory class for hallucinations and negative symptoms (OR 0.77–0.91). Conversely for paranoia, higher education GPS was associated with the most elevated trajectory class (OR 1.25). Trajectory class associations were not significant for schizophrenia, obsessive-compulsive disorder, bipolar disorder, or anorexia GPS. Emotional/behaviour problems and life events in childhood were associated with increased odds of being in the most elevated trajectory class across PENS. Conclusions: Our results suggest latent heterogeneity in the development of paranoia, hallucinations, and negative symptoms in young people that is associated with specific polygenic scores and childhood characteristics. [ABSTRACT FROM AUTHOR]

Background: There is strong evidence of inequalities in mental healthcare access, experiences and outcomes for service users belonging to Black and Asian Minority Ethnic groups experiencing psychosis. Clinicians and academics have speculated that cultural variation in conceptualisations of psychosis, alongside inequitable service provision may explain disparities. There is, however, a dearth of literature exploring this in a South Asian population, despite this ethnic group being the second largest in the United Kingdom. The present study aimed to explore how people from this minority group have experienced and made sense of first‐episode psychosis (FEP). Methods: A qualitative approach was used to explore the lived experience and sense‐making of South Asian individuals experiencing FEP and accessing early intervention services. Eight people were interviewed using a semi‐structured format. The data were analysed using Interpretative Phenomenological Analysis. Results: Three superordinate themes were identified in the group analysis: (1) Disconnection from self and others (2) Doubt and dispute (3) Power and shame. Conclusions: Distinctive ethnic, cultural and systemic influences were strongly evident in how people conceptualized their experiences, how they managed their sense‐making and where they sought support. Experiences were discussed in the context of power and shame, and this research proposes that socio‐cultural context and racialised discourses have an impact on self‐concept, the experiences of help‐seeking (formal and informal), and fundamentally how services help individuals from marginalized communities. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia endophenotypes may help elucidate functional effects of genetic risk variants in multiply affected consanguineous families that segregate recessive risk alleles of large effect size. We studied the association between a schizophrenia risk locus involving a 6.1Mb homozygous region on chromosome 13q22–31 in a consanguineous multiplex family and cognitive functioning, haemodynamic response and white matter integrity using neuroimaging. Methods: We performed CANTAB neuropsychological testing on four affected family members (all homozygous for the risk locus), ten unaffected family members (seven homozygous and three heterozygous) and ten healthy volunteers, and tested neuronal responses on fMRI during an n-back working memory task, and white matter integrity on diffusion tensor imaging (DTI) on four affected and six unaffected family members (four homozygous and two heterozygous) and three healthy volunteers. For cognitive comparisons we used a linear mixed model (Kruskal–Wallis) test, followed by posthoc Dunn's pairwise tests with a Bonferroni adjustment. For fMRI analysis, we counted voxels exceeding the p < 0.05 corrected threshold. DTI analysis was observational. Results: Family members with schizophrenia and unaffected family members homozygous for the risk haplotype showed attention (p < 0.01) and working memory deficits (p < 0.01) compared with healthy controls; a neural activation laterality bias towards the right prefrontal cortex (voxels reaching p < 0.05, corrected) and observed lower fractional anisotropy in the anterior cingulate cortex and left dorsolateral prefrontal cortex. Conclusions: In this family, homozygosity at the 13q risk locus was associated with impaired cognition, white matter integrity, and altered laterality of neural activation. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Large-scale epidemiological and genetic research have shown that psychotic experiences in the community are risk factors for adverse physical and psychiatric outcomes. We investigated the associations of six types of specific psychotic experiences and negative symptoms assessed in mid-adolescence with well-established environmental and genetic risk factors for psychosis. Study Design Fourteen polygenic risk scores (PRS) and nine geographical environmental variables from 3590 participants of the Twins Early Development Study (mean age 16) were associated with paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and negative symptoms scales. The predictors were modeled using LASSO regularization separately (Genetic and Environmental models) and jointly (GE model). Study Results In joint GE models, we found significant genetic associations of negative symptoms with educational attainment PRS (β = −.07; 95% CI = −0.12 to −0.04); cognitive disorganization with neuroticism PRS (β =.05; 95% CI = 0.03–0.08); paranoia with MDD (β =.07; 95% CI = 0.04–0.1), BMI (β =.05; 95% CI = 0.02–0.08), and neuroticism PRS (β =.05; 95% CI = 0.02–0.08). From the environmental measures only family SES (β = −.07, 95% CI = −0.10 to −0.03) and regional education levels (β = −.06; 95% CI = −0.09 to −0.02) were associated with negative symptoms. Conclusions Our findings advance understanding of how genetic propensity for psychiatric, cognitive, and anthropometric traits, as well as environmental factors, together play a role in creating vulnerability for specific psychotic experiences and negative symptoms in mid-adolescence. [ABSTRACT FROM AUTHOR]

Cluster studies identified a subgroup of patients with psychosis whose premorbid adjustment deteriorates before the onset, which may reflect variation in genetic influence. However, other studies reported a complex relationship between distinctive patterns of cannabis use and cognitive and premorbid impairment that is worthy of consideration. We examined whether: (1) premorbid social functioning (PSF) and premorbid academic functioning (PAF) in childhood and adolescence and current intellectual quotient (IQ) define different clusters in 802 first-episode of psychosis (FEP) patients; resulting clusters vary in (2) polygenic risk scores (PRSs) for schizophrenia (SCZ_PRS), bipolar disorder (BD_PRS), major depression (MD_PRS), and IQ (IQ_PRS), and (3) patterns of cannabis use, compared to 1,263 population-based controls. Four transdiagnostic clusters emerged (BIC = 2268.5): (1) high-cognitive-functioning (n  = 205), with the highest IQ (Mean = 106.1, 95% CI: 104.3, 107.9) and PAF, but low PSF. (2) Low-cognitive-functioning (n  = 223), with the lowest IQ (Mean = 73.9, 95% CI: 72.2, 75.7) and PAF, but normal PSF. (3) Intermediate (n  = 224) (Mean_IQ = 80.8, 95% CI: 79.1, 82.5) with low-improving PAF and PSF. 4) Deteriorating (n  = 150) (Mean_IQ = 80.6, 95% CI: 78.5, 82.7), with normal-deteriorating PAF and PSF. The PRSs explained 7.9% of between-group membership. FEP had higher SCZ_PRS than controls [ F (4,1319) = 20.4, P  < .001]. Among the clusters, the deteriorating group had lower SCZ_PRS and was likelier to have used high-potency cannabis daily. Patients with FEP clustered according to their premorbid and cognitive abilities. Pronounced premorbid deterioration was not typical of most FEP, including those more strongly predisposed to schizophrenia, but appeared in a cluster with a history of high-potency cannabis use. [ABSTRACT FROM AUTHOR]