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Background: Pre-diagnostic stages of psychotic illnesses, including 'clinical high risk' (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis. Methods: Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population. Results: Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa. Conclusion: In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population. [ABSTRACT FROM AUTHOR]

BackgroundEvidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.MethodWe used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.ResultsAssociations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.ConclusionsElevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis. [ABSTRACT FROM AUTHOR]

BackgroundThe Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala–prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action.MethodWe employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls.ResultsIrrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met158 allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls.ConclusionsOur results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity. [ABSTRACT FROM PUBLISHER]

There has been extensive discussion of problems of reproducibility of research. Analytical flexibility may contribute to this, by increasing the likelihood that a reported finding represents a chance result. We explored whether analytical flexibility has increased over time, using human imaging studies of bipolar disorder and major depression. Our results indicate that the number of measures collected per study has increased over time for studies of bipolar disorder, but not for studies of major depression. [ABSTRACT FROM PUBLISHER]

Objectives: There is significant overlap between the cortical network involved in fearful face perception and regional abnormalities identified in patients with bipolar disorder. The primary aim of this study was to measure effective connectivity arising from Dynamic Causal Modelling (DCM) to identify differences within this network in a group of patients with bipolar disorder and controls during an affective processing task. Methods: Functional MRI was used to record brain activations from 52 euthymic patients with bipolar disorder and 44 healthy controls engaged in a fearful versus neutral facial affect recognition task. We used Bayesian model selection to identify the best model of effective connectivity, as well as a random-effects analysis. Additionally, the endogenous connections and modulatory influences were extracted and further analyzed. Results: Within the network subserving fearful facial affect recognition, patients with bipolar disorder demonstrated reduced connectivity from the inferior occipital gyrus to the fusiform gyrus compared to healthy controls. Furthermore this connection when modulated by fear showed a reduction in strength in patients with bipolar disorder. Conclusions: Bipolar disorder was associated with deficits early in the processing of facial affect suggesting the possibility of perceptual abnormalities being associated with the disorder. Dr Frangou was supported by a NARSAD Independent Investigator Award [Copyright &y& Elsevier]

Background and aims: Bipolar disorder (BD) is characterised by emotional dysregulation; abnormal emotional information processing is likely to be a component of genetic predisposition to BD. Method: Functional magnetic resonance imaging data was collected during an event-related facial affect recognition task (fearful, angry, sad expressions), from: 41 BDI patients, 22 of their unaffected siblings, and 51 controls. A random effects analysis was implemented using SPM5. Results: Patients, relative to controls had significantly: [a.] reduced activation in the left inferior frontal gyrus and middle occipital gyrus and, [b.] enhanced activation bilaterally in the posterior cingulate and in the left postcentral gyrus; in the temporal lobe, increased activation was seen in the hippocampus and amygdale bilaterally and in the middle and inferior temporal gyri. Siblings, relative to controls showed significantly enhanced activation in the inferior frontal gyrus and in the parahippocampal gyrus and amydgala. Siblings relative to patients had significantly higher activation in the inferior frontal gyrus. Conclusions: In BD patients there is evidence of increased limbic activation and decreased cortical efficiency during facial affect processing; increased ventral PFC activation in siblings, in the presence of increased limbic activation, may serve as a compensatory mechanism mediating resilience to disease expression. [Copyright &y& Elsevier]

Objectives: Working memory (WM) deficits are among the core cognitive abnormalities in schizophrenia. WM is subserved by widely distributed fronto-parietal networks and is undergoing robust development during adolescence. Studying the neural correlates of WM dysfunction in early-onset schizophrenia (EOS) will advance our understanding of aberrant neurodevelopmental processes in the disorder. Method: Nineteen patients with EOS aged 13-19 and 20 matched healthy participants underwent functional Magnetic Resonance Imaging (fMRI) as they performed a N-back verbal WM task with 3 levels of difficulty (1-back, 2-back, 3-back). Following matching for task performance, 14 patients were compared to 20 controls, using non-parametric whole brain and region of interest approaches followed by psycho-physiological interaction analysis (PPI) with seed voxel from the left parietal cluster. Results: Regions within the left prefrontal cortex, the left insula and bilateral anterior cingulate cortex showed reduced activation in EOS patients compared to healthy participants at the 2-back condition. In addition, ROI analysis at the same condition revealed hypoactivation in the EOS group with large effect sizes for left prefrontal and parietal regions. The PPI results revealed negative functional connectivity in the healthy participants’ group but not in EOS between left parietal and right parietal and bilateral frontal regions. Conclusions: Our results support compromised function within the left prefrontal-cingulate network and left insula during the N-Back verbal WM task in patients with EOS compared to healthy participants. They also indicate the possibility of more widespread fronto-parietal network dysfunction, most noted in the left hemisphere in the disorder. [Copyright &y& Elsevier]

Aims: To examine potential similarities in neural activation during the STROOP colour word test (SCWT) in patients with Bipolar Disorder (BD) and their unaffected first degree relatives of BD patients as an expression of genetic predisposition. Methods: 39 remitted BD patients were compared to 46 of their healthy relatives and to 42 controls. fMRI data were collected on a 1.5 T GE Signa MR system using a blocked periodic design and analysed in SPM5. Results: There was no statistically significant group difference in the behavioural performance. At the corrected cluster level threshold of p< 0.001 controls showed more activation than: [a.] BD patients in the caudate, the inferior (BA 47), middle and superior frontal gyri (BA 8, 6, 46), the parietal cortices (BA 7, 40), the precuneus and occipital cortices (BA 7, 19). [b.] Relatives in the caudate and cingulate cortex (BA 24, 31!). No other contrasts were significant. Conclusion: These findings suggest that changes in neural activation during response inhibition may reflect genetic predisposition to BD. [Copyright &y& Elsevier]

Objective: To examine genetic influences the anatomy of the Corpus Callosum (CC) in Bipolar Disorder (BD) by examining first-degree relatives in addition to BD patients. Methods: We compared CCl size and shape in 180 individuals: 70 with BD, 45 of their unaffected first-degree relatives, and 75 healthy controls. The CC was extracted from a mid-sagittal slice from T1-weighted magnetic resonance images; its total area, length and curvature were compared across groups. A non-parametric permutation method was used to examine for alterations in width of the callosum along 39 points. Results: Validating our previous findings, a significant global reduction in CC thickness was seen in BD patients, with a disproportionate thinning in the anterior body. First-degree relatives did not differ in CC size or shape from controls. Duration of illness was associated with thinning in the anterior body, whereas Lithium treatment associated with thicker anterior CC midbody. Conclusions: Global and regional CC thinning is a disease related feature of BD and may not represent a marker of familial disposition. [Copyright &y& Elsevier]

Background: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis., Methods: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models., Results: SI did not predict next-moment fluctuations in PEs, or vice versa . Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs., Conclusions: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

Background: Negative symptoms are one of the most incapacitating features of Schizophrenia but their pathophysiology remains unclear. They have been linked to alterations in grey matter in several brain regions, but findings have been inconsistent. This may reflect the investigation of relatively small patient samples, and the confounding effects of chronic illness and exposure to antipsychotic medication. We sought to address these issues by investigating concurrently grey matter volumes (GMV) and cortical thickness (CTh) in a large sample of antipsychotic-naïve or minimally treated patients with First-Episode Schizophrenia (FES)., Methods: T1-weighted structural MRI brain scans were acquired from 180 antipsychotic-naïve or minimally treated patients recruited as part of the OPTiMiSE study. The sample was stratified into subgroups with ( N = 88) or without ( N = 92) Prominent Negative Symptoms (PMN), based on PANSS ratings at presentation. Regional GMV and CTh in the two groups were compared using Voxel-Based Morphometry (VBM) and FreeSurfer (FS). Between-group differences were corrected for multiple comparisons via Family-Wise Error (FWE) and Monte Carlo z-field simulation respectively at p < 0.05 (2-tailed)., Results: The presence of PMN symptoms was associated with larger left inferior orbitofrontal volume ( p = 0.03) and greater CTh in the left lateral orbitofrontal gyrus ( p = 0.007), but reduced CTh in the left superior temporal gyrus ( p = 0.009)., Conclusions: The findings highlight the role of orbitofrontal and temporal cortices in the pathogenesis of negative symptoms of Schizophrenia. As they were evident in generally untreated FEP patients, the results are unlikely to be related to effects of previous treatment or illness chronicity.

This article examines the significant relationship that existed between commercial British television and the study of animal behaviour. Ethological research provided important content for the new television channel, at the same time as that coverage played a substantial role in creating a new research specialism, the study of primate facial expressions, for this emergent scientific discipline. The key site in this was a television and film unit at London Zoo administered by the Zoological Society and Granada TV. The Granada unit produced 'Animal expressions', a twenty-five-minute television film based on research on monkeys and apes by the Dutch postgraduate student and soon-to-be-leading-authority Jan van Hooff. Recovering the production and multiple uses of 'Animal expressions', this paper offers the first sustained historical analysis of science on commercial television. I show how Granada patronage helped Van Hooff to support his argument that human expressions such as smiling and laughter shared common evolutionary origins with similar facial movements in nonhuman primates. Emphasizing the mutual shaping of science and ITV, I argue that 'Animal expressions' repurposed televisual conventions of framing talking heads, and blended serious science with the comedy of 'funny faces', thereby epitomizing Granada's public-service strategy at a time when commercial television was defending itself from criticism in the Pilkington report.

Aims: Childhood trauma is associated with an elevated risk for psychosis, but the psychological mechanisms involved remain largely unclear. This study aimed to investigate emotional and psychotic stress reactivity in daily life as a putative mechanism linking childhood trauma and clinical outcomes in individuals at ultra-high-risk (UHR) for psychosis., Methods: Experience sampling methodology was used to measure momentary stress, affect and psychotic experiences in the daily life of N = 79 UHR individuals in the EU-GEI High Risk Study. The Childhood Trauma Questionnaire was used to assess self-reported childhood trauma. Clinical outcomes were assessed at baseline, 1- and 2-year follow-up., Results: The association of stress with positive (β = -0.14, p = 0.010) and negative affect (β = 0.11, p = 0.020) was modified by transition status such that stress reactivity was greater in individuals who transitioned to psychosis. Moreover, the association of stress with negative affect (β = 0.06, p = 0.019) and psychotic experiences (β = 0.05, p = 0.037) was greater in individuals exposed to high v. low levels of childhood trauma. We also found evidence that decreased positive affect in response to stress was associated with reduced functioning at 1-year follow-up (B = 6.29, p = 0.034). In addition, there was evidence that the association of childhood trauma with poor functional outcomes was mediated by stress reactivity (e.g. indirect effect: B = -2.13, p = 0.026), but no evidence that stress reactivity mediated the association between childhood trauma and transition (e.g. indirect effect: B = 0.14, p = 0.506)., Conclusions: Emotional and psychotic stress reactivity may be potential mechanisms linking childhood trauma with clinical outcomes in UHR individuals.

Background: Risk prediction algorithms have long been used in health research and practice (e.g. prediction of cardiovascular disease and diabetes). However, similar tools have not been developed for mental health. For example, for psychotic disorders, attempts to sum environmental risk are rare, unsystematic and dictated by available data. In light of this, we sought to develop a valid, easy to use measure of the aggregate environmental risk score (ERS) for psychotic disorders., Methods: We reviewed the literature to identify well-replicated and validated environmental risk factors for psychosis that combine a significant effect and large-enough prevalence. Pooled estimates of relative risks were taken from the largest available meta-analyses. We devised a method of scoring the level of exposure to each risk factor to estimate ERS. Relative risks were rounded as, due to the heterogeneity of the original studies, risk effects are imprecisely measured., Results: Six risk factors (ethnic minority status, urbanicity, high paternal age, obstetric complications, cannabis use and childhood adversity) were used to generate the ERS. A distribution for different levels of risk based on simulated data showed that most of the population would be at low/moderate risk with a small minority at increased environmental risk for psychosis., Conclusions: This is the first systematic approach to develop an aggregate measure of environmental risk for psychoses in asymptomatic individuals. This can be used as a continuous measure of liability to disease; mostly relevant to areas where the original studies took place. Its predictive ability will improve with the collection of additional, population-specific data.