Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin.

Abnormalities in functional brain networks (functional connectome) are increasingly implicated in people at Clinical High Risk for Psychosis (CHR-P). Intranasal oxytocin, a potential novel treatment for the CHR-P state, modulates network topology in healthy individuals. However, its connectomic effects in people at CHR-P remain unknown. Forty-seven men (30 CHR-P and 17 healthy controls) received acute challenges of both intranasal oxytocin 40 IU and placebo in two parallel randomised, double-blind, placebo-controlled cross-over studies which had similar but not identical designs. Multi-echo resting-state fMRI data was acquired at approximately 1 h post-dosing. Using a graph theoretical approach, the effects of group (CHR-P vs healthy control), treatment (oxytocin vs placebo) and respective interactions were tested on graph metrics describing the topology of the functional connectome. Group effects were observed in 12 regions (all pFDR < 0.05) most localised to the frontoparietal network. Treatment effects were found in 7 regions (all pFDR < 0.05) predominantly within the ventral attention network. Our major finding was that many effects of oxytocin on network topology differ across CHR-P and healthy individuals, with significant interaction effects observed in numerous subcortical regions strongly implicated in psychosis onset, such as the thalamus, pallidum and nucleus accumbens, and cortical regions which localised primarily to the default mode network (12 regions, all pFDR < 0.05). Collectively, our findings provide new insights on aberrant functional brain network organisation associated with psychosis risk and demonstrate, for the first time, that oxytocin modulates network topology in brain regions implicated in the pathophysiology of psychosis in a clinical status (CHR-P vs healthy control) specific manner.

Monitoring Daily Sleep, Mood, and Affect Using Digital Technologies and Wearables: A Systematic Review.

Background: Sleep and affective states are closely intertwined. Nevertheless, previous methods to evaluate sleep-affect associations have been limited by poor ecological validity, with a few studies examining temporal or dynamic interactions in naturalistic settings. Objectives: First, to update and integrate evidence from studies investigating the reciprocal relationship between daily sleep and affective phenomena (mood, affect, and emotions) through ambulatory and prospective monitoring. Second, to evaluate differential patterns based on age, affective disorder diagnosis (bipolar, depression, and anxiety), and shift work patterns on day-to-day sleep-emotion dyads. Third, to summarise the use of wearables, actigraphy, and digital tools in assessing longitudinal sleep-affect associations. Method: A comprehensive PRISMA-compliant systematic review was conducted through the EMBASE, Ovid MEDLINE(R), PsycINFO, and Scopus databases. Results: Of the 3024 records screened, 121 studies were included. Bidirectionality of sleep-affect associations was found (in general) across affective disorders (bipolar, depression, and anxiety), shift workers, and healthy participants representing a range of age groups. However, findings were influenced by the sleep indices and affective dimensions operationalised, sampling resolution, time of day effects, and diagnostic status. Conclusions: Sleep disturbances, especially poorer sleep quality and truncated sleep duration, were consistently found to influence positive and negative affective experiences. Sleep was more often a stronger predictor of subsequent daytime affect than vice versa. The strength and magnitude of sleep-affect associations were more robust for subjective (self-reported) sleep parameters compared to objective (actigraphic) sleep parameters.

Clozapine augmentation with long-acting antipsychotic injections: A case series and systematic review.

BACKGROUND: Up to 30% of patients with a diagnosis of treatment-resistant psychosis remain symptomatic despite an optimal trial with the gold standard treatment, clozapine. Emerging evidence suggests the clinical utility of long-acting injections (LAI) in such clinical scenarios. In this study, we aimed to describe clozapine augmentation with LAIs in an inner London hospital and explore the literature on the clinical effectiveness of this treatment modality. METHODS: Patients prescribed clozapine, who were commenced on a LAI between 2007 and 2023 by the United Kingdom's largest mental health trust, were identified from electronic patient records. First, routine clinical data were used to describe the use, effectiveness, and safety of this augmentation strategy. Second, we conducted a literature search up to 1st June 2023 to identify published studies describing clinical outcomes after clozapine augmentation with a LAI. Clinical outcomes were collated and presented in a table, including hospitalisation rates and quantitative clinical assessments using validated scales. RESULTS: Of the 1248 patients prescribed clozapine in SLaM, three patients (0.2%) received augmentation with the following LAIs: olanzapine embonate, paliperidone palmitate and pipotiazine palmitate. This treatment strategy was clinically effective and generally well tolerated in all three cases. Twelve published studies between 2010 and 2022 were included in the review. Eight distinct LAIs were reported (4 first and 4 second generation antipsychotics), with risperidone and paliperidone most widely studied. All the identified studies were observational including mirror-image studies, case series and case reports. Duration of follow up varied from 3 months to 3 years. There was evidence that the use of LAIs with clozapine can significantly reduce clinical symptoms, hospitalisation rates and bed days. No serious adverse effects were reported. CONCLUSION: This preliminary evidence suggests clinical utility of LAIs in alleviating residual symptoms and subsequently reducing hospitalisation rates in patients optimised on clozapine treatment. The current study warrants further investigations including a randomised controlled study to establish the clinical efficacy, tolerability, and place in therapy of this treatment modality.

Effects of psychosis-associated genetic markers on brain volumetry: a systematic review of replicated findings and an independent validation.

BACKGROUND: Given psychotic illnesses' high heritability and associations with brain structure, numerous neuroimaging-genetics findings have been reported in the last two decades. However, few findings have been replicated. In the present independent sample we aimed to replicate any psychosis-implicated SNPs (single nucleotide polymorphisms), which had previously shown at least two main effects on brain volume. METHODS: A systematic review for SNPs showing a replicated effect on brain volume yielded 25 studies implicating seven SNPs in five genes. Their effect was then tested in 113 subjects with either schizophrenia, bipolar disorder, 'at risk mental state' or healthy state, for whole-brain and region-of-interest (ROI) associations with grey and white matter volume changes, using voxel-based morphometry. RESULTS: We found FWER-corrected (Family-wise error rate) (i.e. statistically significant) associations of: (1) CACNA1C-rs769087-A with larger bilateral hippocampus and thalamus white matter, across the whole brain; and (2) CACNA1C-rs769087-A with larger superior frontal gyrus, as ROI. Higher replication concordance with existing literature was found, in decreasing order, for: (1) CACNA1C-rs769087-A, with larger dorsolateral-prefrontal/superior frontal gyrus and hippocampi (both with anatomical and directional concordance); (2) ZNF804A-rs11681373-A, with smaller angular gyrus grey matter and rectus gyri white matter (both with anatomical and directional concordance); and (3) BDNF-rs6265-T with superior frontal and middle cingulate gyri volume change (with anatomical and allelic concordance). CONCLUSIONS: Most literature findings were not herein replicated. Nevertheless, high degree/likelihood of replication was found for two genome-wide association studies- and one candidate-implicated SNPs, supporting their involvement in psychosis and brain structure.

Social isolation and psychosis: an investigation of social interactions and paranoia in daily life.

Social isolation has been suggested to foster paranoia. Here we investigate whether social company (i.e., being alone vs. not) and its nature (i.e., stranger/distant vs. familiar other) affects paranoia differently depending on psychosis risk. Social interactions and paranoid thinking in daily life were investigated in 29 patients with clinically stable non-affective psychotic disorders, 20 first-degree relatives, and 26 controls (n = 75), using the experience sampling method (ESM). ESM was completed up to ten times daily for 1 week. Patients experienced marginally greater paranoia than relatives [b = 0.47, p = 0.08, 95% CI (- 0.06, 1.0)] and significantly greater paranoia than controls [b = 0.55, p = 0.03, 95% CI (0.5, 1.0)], but controls and relatives did not differ [b = 0.07, p = 0.78, 95% CI (- 0.47, 0.61)]. Patients were more often alone [68.5% vs. 44.8% and 56.2%, respectively, p = 0.057] and experienced greater paranoia when alone than when in company [b = 0.11, p = 0.016, 95% CI (0.02, 0.19)]. In relatives this was reversed [b = - 0.17, p < 0.001, 95% CI (- 0.28, - 0.07)] and in controls non-significant [b = - 0.02, p = 0.67, 95% CI (- 0.09, 0.06)]. The time-lagged association between being in social company and subsequent paranoia was non-significant and paranoia did not predict the likelihood of being in social company over time (both p's = 0.68). All groups experienced greater paranoia in company of strangers/distant others than familiar others [X2(2) = 4.56, p = 0.03] and being with familiar others was associated with lower paranoia over time [X2(2) = 4.9, p = 0.03]. Patients are frequently alone. Importantly, social company appears to limit their paranoia, particularly when being with familiar people. The findings stress the importance of interventions that foster social engagement and ties with family and friends.

A Novel Virtual Reality Assessment of Functional Cognition: Validation Study.

BACKGROUND: Cognitive deficits are present in several neuropsychiatric disorders, including Alzheimer disease, schizophrenia, and depression. Assessments used to measure cognition in these disorders are time-consuming, burdensome, and have low ecological validity. To address these limitations, we developed a novel virtual reality shopping task-VStore. OBJECTIVE: This study aims to establish the construct validity of VStore in relation to the established computerized cognitive battery, Cogstate, and explore its sensitivity to age-related cognitive decline. METHODS: A total of 142 healthy volunteers aged 20-79 years participated in the study. The main VStore outcomes included verbal recall of 12 grocery items, time to collect items, time to select items on a self-checkout machine, time to make the payment, time to order coffee, and total completion time. Construct validity was examined through a series of backward elimination regression models to establish which Cogstate tasks, measuring attention, processing speed, verbal and visual learning, working memory, executive function, and paired associate learning, in addition to age and technological familiarity, best predicted VStore performance. In addition, 2 ridge regression and 2 logistic regression models supplemented with receiver operating characteristic curves were built, with VStore outcomes in the first model and Cogstate outcomes in the second model entered as predictors of age and age cohorts, respectively. RESULTS: Overall VStore performance, as indexed by the total time spent completing the task, was best explained by Cogstate tasks measuring attention, working memory, paired associate learning, and age and technological familiarity, accounting for 47% of the variance. In addition, with λ=5.16, the ridge regression model selected 5 parameters for VStore when predicting age (mean squared error 185.80, SE 19.34), and with λ=9.49 for Cogstate, the model selected all 8 tasks (mean squared error 226.80, SE 23.48). Finally, VStore was found to be highly sensitive (87%) and specific (91.7%) to age cohorts, with 94.6% of the area under the receiver operating characteristic curve. CONCLUSIONS: Our findings suggest that VStore is a promising assessment that engages standard cognitive domains and is sensitive to age-related cognitive decline.

A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia.

BACKGROUND: Transcranial magnetic stimulation can be combined with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) to evaluate the excitatory and inhibitory functions of the cerebral cortex in a standardized manner. It has been postulated that schizophrenia is a disorder of functional neural connectivity underpinned by a relative imbalance of excitation and inhibition. The aim of this review was to provide a comprehensive overview of TMS-EMG and TMS-EEG research in schizophrenia, focused on excitation or inhibition, connectivity, motor cortical plasticity and the effect of antipsychotic medications, symptom severity and illness duration on TMS-EMG and TMS-EEG indices. METHODS: We searched PsycINFO, Embase and Medline, from database inception to April 2020, for studies that included TMS outcomes in patients with schizophrenia. We used the following combination of search terms: transcranial magnetic stimulation OR tms AND interneurons OR glutamic acid OR gamma aminobutyric acid OR neural inhibition OR pyramidal neurons OR excita* OR inhibit* OR GABA* OR glutam* OR E-I balance OR excitation-inhibition balance AND schizoaffective disorder* OR Schizophrenia OR schizophreni*. RESULTS: TMS-EMG and TMS-EEG measurements revealed deficits in excitation or inhibition, functional connectivity and motor cortical plasticity in patients with schizophrenia. Increased duration of the cortical silent period (a TMS-EMG marker of γ-aminobutyric acid B receptor activity) with clozapine was a relatively consistent finding. LIMITATIONS: Most of the studies used patients with chronic schizophrenia and medicated patients, employed cross-sectional group comparisons and had small sample sizes. CONCLUSION: TMS-EMG and TMS-EEG offer an opportunity to develop a novel and improved understanding of the physiologic processes that underlie schizophrenia and to assess the therapeutic effect of antipsychotic medications. In the future, these techniques may also help predict disease progression and further our understanding of the excitatory/inhibitory balance and its implications for mechanisms that underlie treatment-resistant schizophrenia.

Attachment styles moderate Theory of Mind differences between persons with schizophrenia, first-degree relatives and controls.

OBJECTIVES: Theory of Mind (ToM) plays a role in social functioning and is impaired in patients with schizophrenia and to a lesser degree in first-degree relatives, compared to healthy controls. This study investigates whether attachment styles moderate these observed group differences in ToM. METHODS: This cross-sectional study included a sample of 51 patients, 23 first-degree relatives, and 49 controls who completed assessments of anxious and avoidant attachment (Psychosis Attachment Measure), ToM (Reading the Mind in the Eyes Test), and estimated cognitive ability. Patients' symptoms were assessed with the Positive and Negative Syndrome Scale. RESULTS: Patients differed from controls and relatives in ToM performance but not in attachment avoidance or attachment anxiety. Attachment anxiety showed an interaction with group over ToM. The interaction was significant only between patients and controls but not between patients and relatives or relatives and controls. Post-hoc analysis showed that patients and controls showed differential ToM performance at average and high attachment anxiety. In patients, symptom levels did not moderate the association between attachment and ToM. CONCLUSIONS: Attachment anxiety is related to poorer levels of ToM in patients, suggesting this may have a contributory role in schizophrenia. The findings stress the need for longitudinal research into the directionality of the relationship between ToM and attachment anxiety. PRACTITIONER POINTS: Relationships with significant others might be a factor that influences the way in which social information is processed by persons with a diagnosis of a psychotic disorder. In patients, higher levels of attachment anxiety - that is, low self-worth, fear of abandonment and rejection, continuous vigilance of threat-related cues - were associated with a lower ability to understand the mental states of others. However, at lower levels of attachment anxiety, their ToM performance was comparable to that of relatives and controls. This effect was not influenced by symptom severity. Further research is required to confirm the potential influence of attachment insecurity on ToM ability as the latter is strongly related to patient's functional outcomes.

A retrospective study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis.

BACKGROUND: Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored. AIMS: This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period. METHOD: Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication. RESULTS: Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14-1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11-1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling. CONCLUSIONS: Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.

Cognitive remediation for inpatients with psychosis: a systematic review and meta-analysis.

Cognitive difficulties are common in people with psychosis and associated with considerable disability. Cognitive remediation (CR) can reduce the burden of cognitive difficulties and improve functioning. While mental health care has predominantly shifted to the community, people with greater illness severity and complexity, and those with poor response to treatment and concomitant greater cognitive difficulties, continue to receive inpatient care. The aim of this study is to review and evaluate the acceptability and efficacy of CR for inpatients with psychosis. A systematic search was used to identify randomized controlled trials of CR for inpatients with psychosis. Demographic and clinical information was extracted by independent raters together with therapy outcomes. Study quality was assessed using the Cochrane Collaboration Risk of Bias Assessment tool. Standardized mean change for cognitive and functional outcomes was calculated using Hedges's g and used to infer therapy effects with meta-analysis. Twenty studies were identified considering 1509 participants. Results from random-effect models suggested that CR was effective in improving processing speed (g = 0.48), memory (g = 0.48) and working memory (g = 0.56). While there was an indication of improvements in the levels of vocational, social and global functioning, these were less reliable. On average, 7% of participants dropped-out of treatment. Studies methodological quality was moderate. CR is an acceptable intervention for inpatients with psychosis and can lead to significant cognitive improvements. Evidence for improvement in functioning requires more robust and converging evidence. Future research should extend the evaluation of inpatient CR to subsequent post-discharge community functioning and further need for care.

Understanding misidentification syndromes using the integrative memory model.

Misidentification syndromes occur commonly in neuropsychiatric practice and can be explained through aberrant integration of recollection and familiarity, in keeping with a dysfunction at the level of the attributional system in the new integrative memory model. We examine neuroimaging findings associated with Fregoli and Capgras syndromes and compare these with the proposed neural substrate of the integrative memory model supporting the core and attribution functions.

When trust is lost: the impact of interpersonal trauma on social interactions.

BACKGROUND: Trauma due to deliberate harm by others is known to increase the likelihood of developing Post-Traumatic Stress Disorder (PTSD). This is the first study investigating basic and dynamic trust in 'interpersonal' PTSD. METHODS: Thirty-two participants with PTSD and 22 healthy controls played a novel multi-round version of a monetary investment protocol, the so-called 'Trust Game', a task from the behavioural economics literature, which is considered to involve trust and reciprocity. We used two 'Trust Games' including cooperative and unfair partners. RESULTS: Findings showed an effect for lower basic investment in PTSD compared to healthy controls, that trended towards significance (p = 0.09). All participants showed behavioural flexibility and modified their trust based on behavioural cues from their cooperative and unfair game partners. However, participants with PTSD made significantly lower investments towards the cooperative partner than controls. Investments towards the unfair partner did not differ between groups. Higher trauma scores were associated with lower levels of trust-related investments towards the cooperative but not the unfair game partner. CONCLUSION: The association between reduced trust towards cooperative others in individuals who experienced interpersonal trauma could indicate acquired insensitivity to social rewards or inflexible negative beliefs about others as a sequel of the traumatic experience, which increases in a dose response relationship with the severity of the trauma. A specific focus on cooperation and trusting behaviour could provide a treatment target for future cognitive and pharmacological interventions.

Hope or hype in the treatment of schizophrenia - what's the role of the physician?

According to the experience of people with schizophrenia, their psychiatrists' attitude towards the outcome of their illness is lacking in hope, which directly affects mutual faith in treatment. Here we discuss the scientific basis of hope and show its instrumental role in optimising the best treatment strategies for schizophrenia. Declaration of interest R.A.B has received honoraria for educational input and non-financial support from Ache; honoraria for educational input from Lundbeck; grants, honoraria for educational input and non-financial support from Janssen; all outside the submitted work. G.E.M.G. has received honoraria for educational input and non-financial support from Janssen outside the submitted work. G.M. reports support from Janssen-Cilag, outside the submitted work, and is an employee at Janssen-Cilag. S.S. has received grants and honoraria for educational input from EnVivo Pharmaceuticals, Takeda, AbbVie and Janssen Pharmaceuticals, outside the submitted work.

Differential neural reward mechanisms in treatment-responsive and treatment-resistant schizophrenia.

BACKGROUND: The significant proportion of schizophrenia patients refractory to treatment, primarily directed at the dopamine system, suggests that multiple mechanisms may underlie psychotic symptoms. Reinforcement learning tasks have been employed in schizophrenia to assess dopaminergic functioning and reward processing, but these have not directly compared groups of treatment-refractory and non-refractory patients. METHODS: In the current functional magnetic resonance imaging study, 21 patients with treatment-resistant schizophrenia (TRS), 21 patients with non-treatment-resistant schizophrenia (NTR), and 24 healthy controls (HC) performed a probabilistic reinforcement learning task, utilizing emotionally valenced face stimuli which elicit a social bias toward happy faces. Behavior was characterized with a reinforcement learning model. Trial-wise reward prediction error (RPE)-related neural activation and the differential impact of emotional bias on these reward signals were compared between groups. RESULTS: Patients showed impaired reinforcement learning relative to controls, while all groups demonstrated an emotional bias favoring happy faces. The pattern of RPE signaling was similar in the HC and TRS groups, whereas NTR patients showed significant attenuation of RPE-related activation in striatal, thalamic, precentral, parietal, and cerebellar regions. TRS patients, but not NTR patients, showed a positive relationship between emotional bias and RPE signal during negative feedback in bilateral thalamus and caudate. CONCLUSION: TRS can be dissociated from NTR on the basis of a different neural mechanism underlying reinforcement learning. The data support the hypothesis that a favorable response to antipsychotic treatment is contingent on dopaminergic dysfunction, characterized by aberrant RPE signaling, whereas treatment resistance may be characterized by an abnormality of a non-dopaminergic mechanism - a glutamatergic mechanism would be a possible candidate.

Stimulating thought: a functional MRI study of transcranial direct current stimulation in schizophrenia.

Individuals with schizophrenia typically suffer a range of cognitive deficits, including prominent deficits in working memory and executive function. These difficulties are strongly predictive of functional outcomes, but there is a paucity of effective therapeutic interventions targeting these deficits. Transcranial direct current stimulation is a novel neuromodulatory technique with emerging evidence of potential pro-cognitive effects; however, there is limited understanding of its mechanism. This was a double-blind randomized sham controlled pilot study of transcranial direct current stimulation on a working memory (n-back) and executive function (Stroop) task in 28 individuals with schizophrenia using functional magnetic resonance imaging. Study participants received 30 min of real or sham transcranial direct current stimulation applied to the left frontal cortex. The 'real' and 'sham' groups did not differ in online working memory task performance, but the transcranial direct current stimulation group demonstrated significant improvement in performance at 24 h post-transcranial direct current stimulation. Transcranial direct current stimulation was associated with increased activation in the medial frontal cortex beneath the anode; showing a positive correlation with consolidated working memory performance 24 h post-stimulation. There was reduced activation in the left cerebellum in the transcranial direct current stimulation group, with no change in the middle frontal gyrus or parietal cortices. Improved performance on the executive function task was associated with reduced activity in the anterior cingulate cortex. Transcranial direct current stimulation modulated functional activation in local task-related regions, and in more distal nodes in the network. Transcranial direct current stimulation offers a potential novel approach to altering frontal cortical activity and exerting pro-cognitive effects in schizophrenia.

Hearts and Minds: Real-Life Cardiotoxicity With Clozapine in Psychosis.

BACKGROUND: Schizophrenia has a 1% prevalence in the population; 30% of these patients are treatment refractory. Clozapine is the only drug licensed to treat treatment refractory psychosis, but concerns about potential adverse effects result in only a proportion of eligible patients being treated. Although a well-documented neutropenia risk is mitigated by routine blood testing, cardiac toxicity is a commonly cited reason to discontinue clozapine treatment. However, there is little data on the real-life cardiac outcomes in those receiving clozapine treatment. METHODS: Retrospective review of electrocardiogram, echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory schizophrenia, treated with clozapine and other antipsychotic medication, referred for cardiology opinion. RESULTS: Commonest reasons for referral were development of left ventricular (LV) impairment or sinus tachycardia with normal LV function. Patients were reviewed by a range of cardiologists, receiving varied interventions.Median LV ejection fraction in the clozapine group was normal (52%). Serial echocardiograms demonstrated that clozapine-treated patients with LV impairment had no change in LV ejection fraction over a 4-month follow-up. Left ventricular ejection fraction did not differ between patients treated with clozapine and other antipsychotics. However, over an 11-year follow-up period, 48% of patients had discontinued clozapine treatment. CONCLUSIONS: This naturalistic study demonstrates that clozapine is not associated with significant cardiac mortality or morbidity. There is a real need for multidisciplinary working between specialist cardiologists and psychiatrists caring for these complex patients to facilitate optimal long-term physical and mental health outcomes.

Post graduate clinical placements: evaluating benefits and challenges with a mixed methods cross sectional design.

BACKGROUND: Systematic evaluations of clinical placements are rare, especially when offered alongside academic postgraduate courses. An evidence-based approach is important to allow pedagogically-driven provision, rather than that solely governed by opinion or market demand. Our evaluation assessed a voluntary clinical placement scheme allied to a mental health course. METHODS: Data were collected over academic years 2010/11- 2013/14, from participating students (n = 20 to 58) and clinician supervisors (n = 10-12), using a mixed-methods cross-sectional design. Quantitative evaluation captured information on uptake, dropout, resource use, attitudes and experience, using standardized (the Placement Evaluation Questionnaire; the Scale To Assess the Therapeutic Relationship - Clinical version and the University of Toronto Placement Supervisor Evaluation) and bespoke questionnaires and audit data. Qualitative evaluation comprised two focus groups (5 clinicians, 5 students), to investigate attitudes, experience, perceived benefits, disadvantages and desired future developments. Data were analysed using framework analysis to identify a priori and emergent themes. RESULTS: High uptake (around 70 placements per annum), low dropout (2-3 students per annum; 5 %) and positive focus group comments suggested placements successfully provided added value and catered sufficiently to student demand. Students' responses confirmed that placements met expectations and the perception of benefit remained after completion with 70 % (n = 14) reporting an overall positive experience, 75 % (n = 15) reporting a pleasant learning experience, 60 % (n = 12) feeling that their clinical skills were enhanced and 85 % (n = 17) believing that it would benefit other students. Placements contributed the equivalent of seven full time unskilled posts per annum to local health care services. While qualitative data revealed perceived 'mutual benefit' for both students and clinicians, this was qualified by the inherent limitations of students' time and expertise. Areas for development included fostering learning around professionalism and students' confidence on placement. CONCLUSIONS: The addition of healthcare placements to academic postgraduate taught courses can improve their attractiveness to applicants, benefit healthcare services and enhance students' perception of their learning experiences. Well-positioned and supported placement learning opportunities could become a key differentiator for academic courses, over potential competitors. However, the actual implications for student employability and achievement remain to be established.

Neurophysiological effects of acute oxytocin administration: systematic review and meta-analysis of placebo-controlled imaging studies.

BACKGROUND: Oxytocin (OXT) plays a prominent role in social cognition and may have clinical applications for disorders such as autism, schizophrenia and social anxiety. The neural basis of its mechanism of action remains unclear. METHODS: We conducted a systematic literature review of placebo-controlled imaging studies using OXT as a pharmacological manipulator of brain activity. RESULTS: We identified a total of 21 studies for inclusion in our review, and after applying additional selection criteria, 11 of them were included in our fMRI voxel-based meta-analysis. The results demonstrate consistent alterations in activation of brain regions, including the temporal lobes and insula, during the processing of social stimuli, with some variation dependent on sex and task. The meta-analysis revealed significant left insular hyperactivation after OXT administration, suggesting a potential modulation of neural circuits underlying emotional processing. LIMITATIONS: This quantitative review included only a limited number of studies, thus the conclusions of our analysis should be interpreted cautiously. This limited sample size precluded a more detailed exploration of potential confounding factors, such as sex or other demographic factors, that may have affected our meta-analysis. CONCLUSION: Oxytocin has a wide range of effects over neural activity in response to social and emotional processing, which is further modulated by sex and task specificity. The magnitude of this neural activation is largest in the temporal lobes, and a meta-analysis across all tasks and both sexes showed that the left insula demonstrated the most robust activation to OXT administration.

I spy with my little eye - the detection of intentional contingency in early psychosis.

INTRODUCTION: Paranoid delusions have been associated with a tendency to over-attribute intentionality and contingency to others' actions and incidental events in individuals with chronic psychosis. However, this hyper-associative perception bias has not been investigated in the early illness stages of psychosis, during which it may play a particularly crucial role in the formation of symptoms. METHOD: We used an experimental paradigm with 20 short film clips of simple animate and inanimate shapes that either moved in a contingent or non-contingent manner to investigate the perception of contingency in 38 adolescents with early psychosis and 93 healthy control adolescents. Participants rated the contingency between the shapes' movements on a scale from 0 to 10. The data were analysed with multilevel regression analyses to account for repeated measures within subjects. RESULTS: There were no significant differences between patients and controls; both perceived the contingency of the shapes' movements similarly across all conditions and patients' contingency perception was unrelated to their levels of paranoid delusions. CONCLUSION: Contingency perception was unimpaired in patients with early psychosis, suggesting that it might still be intact in the early illness stages. Future studies should set out to determine whether the early illness stages could offer a window for interventions that counteract the development of hyper-associative perceptions of contingency.