Mental Health Partnership NHS Trust, Epping, UK Summary

The functional anatomy of divided attentio

The impact of CACNA1C gene, and its epistasis with ZNF804A, on white matter microstructure in health, schizophrenia and bipolar disorder

Genome-wide studies have identified allele A (adenine) of single nucleotide polymorphism (SNP) rs1006737 of the calcium-channel CACNA1C gene as a risk factor for both schizophrenia (SZ) and bipolar disorder (BD) as well as allele A for rs1344706 in the zinc-finger ZNF804A gene. These illnesses have also been associated with white matter abnormalities, reflected by reductions in fractional anisotropy (FA), measured using diffusion tensor imaging (DTI). We assessed the impact of the CACNA1C psychosis risk variant on FA in SZ, BD and health. 230 individuals (with existing ZNF804A rs1344706 genotype data) were genotyped for CACNA1C rs1006737 and underwent DTI. FA data was analysed with tract-based spatial statistics and threshold-free cluster enhancement significance correction (p < 0.05) to detect effects of CACNA1C genotype on FA, and its potential interaction with ZNF804A genotype and with diagnosis, on FA. There was no significant main effect of the CACNA1C genotype on FA, nor diagnosis by genotype(s) interactions. Nevertheless, when inspecting SZ in particular, risk allele carriers had significantly lower FA than the protective genotype individuals, in portions of the left middle occipital and parahippocampal gyri, right cerebelleum, left optic radiation and left inferior and superior temporal gyri. Our data suggests a minor involvement of CACNA1C rs1006737 in psychosis via conferring susceptibility to white matter microstructural abnormalities in SZ. Put in perspective, ZNF804A rs1344706, not only had a significant main effect, but its SZ-specific effects were two orders of magnitude more widespread than that of CACNA1C rs1006737

Sensory Attenuation Assessed by Sensory Evoked Potentials in Functional Movement Disorders.

BACKGROUND: Functional (psychogenic) movement disorders (FMD) have features associated with voluntary movement (e.g. distractibility) but patients report movements to be out of their control. One explanation for this phenomenon is that sense of agency for movement is impaired. The phenomenon of reduction in the intensity of sensory experience when movement is self-generated and a reduction in sensory evoked potentials (SEPs) amplitude at the onset of self-paced movement (sensory attenuation) have been linked to sense of agency for movement. METHODS: We compared amplitude of SEPs from median nerve stimulation at rest and at the onset of a self-paced movement of the thumb in 17 patients with FMD and 17 healthy controls. RESULTS: Patients showed lack of attenuation of SEPs at the onset of movement compared to reduction in amplitude of SEPs in controls. FMD patients had significantly different ratios of movement onset to rest SEPs than did healthy controls at each electrode: 0.79 in healthy controls and 1.35 in patients at F3 (t = -4.22, p<0.001), 0.78 in healthy controls and 1.12 at patients C3 (t = -3.15, p = 0.004) and 0.77 in healthy controls and 1.05 at patients P3 (t = -2.88, p = 0.007). CONCLUSIONS: Patients with FMD have reduced sensory attenuation as measured by SEPs at onset of self-paced movement. This finding can be plausibly linked to impairment of sense of agency for movement in these patients

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

The role of expecting feedback during decision-making under risk

Sometimes choice is followed by outcome feedback and other times it is not. It remains unknown whether humans prefer gambling when they expect feedback to be revealed. Regarding this question, decision-making theories make alternative predictions. Some theories have proposed that choice is influenced by whether one expects to be disappointed in the future. Given that feedback is sometimes disappointing, these theories predict increased aversion towards gambling when feedback is expected compared to when feedback is not expected. The opposite effect is predicted by theories of curiosity, which postulate reduction of uncertainty as an important behavioural drive. Given that feedback reduces uncertainty, these theories predict that gambling will be favoured when feedback is expected. To examine whether expecting feedback influences gambling behaviour, we recorded functional neuroimaging data while participants performed a novel decision-making task requiring to chose between a sure option and a gamble. Crucially, participants expected to receive feedback in some trials but not in other trials. Consistent with theories of curiosity, we found that expecting feedback increased gambling propensity. At the neural level, at option presentation the increased value of gambling during feedback was reflected in activity in the ventral striatum. This suggests that, together with its established role in signalling reward, the ventral striatum also processes a form of epistemic value. Our study demonstrates that gambling becomes more attractive when feedback is expected and suggests that striatal activity could signal the value of feedback information

Importance of GNSS data quality assessment with novel control criteria in professional soccer match- play

This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Performance Analysis in Sport on 06/07/2021, available online: https://doi.org/10.1080/24748668.2021.1947017This study assessed the quality of Global Navigation Satellite System (GNSS) signal during professional football match-play in different stadia with the application of a novel Data Quality Control Criteria (DQCC). DQCC was applied to GPS-files from match-play, derived using 10 Hz GNSS devices for 27 professional soccer players across a season to assess external load measures accounting for poor positioning quality (%) and horizontal dilution of precision. Performances were categorised on playing position as Wide or Central to assess proximity to stand cover on GNSS signal quality. An average reduction in total distance (11.2%), high-speed running distance (6.4%), sprint distance (7.0%), accelerations (10.3%) and decelerations (10.0%) (all P <0.01) was observed upon DQCC application. In worst cases, 90% of an external variable was affected by poor quality signal. Signal quality was worse for wide positioned players than centrally positioned (positioning quality 2.6% lower (P <0.01)), resulting in a larger reduction of external variables upon DQCC application. Large stands in football stadia affect the data quality of GNSS and is exacerbated for players positioned closer to stand cover. Viewing only data with acceptable Position Quality and HDOP meaningfully reduces measured external loads, which has implications for the application of match data

Are we failing clinical trials? A case for strong aggregate outcomes

Clinical trials in psychiatry inherit methods for design and statistical analysis from evidence-based medicine. However, trials in other clinical disciplines benefit from a more specific relationship between instruments that measure disease state (e.g. biomarkers, clinical signs), the underlying pathology and diagnosis such that primary outcomes can be readily defined. Trials in psychiatry use diagnosis (i.e. a categorical label for a syndrome) as a proxy for the underlying disorder, and outcomes are defined, for example, as a percentage change in a univariate total score on some clinical instrument. We label this approach to defining outcomes weak aggregation of disease state. Univariate measures are necessary, because statistical methodology is both tractable and well-developed for scalar outcomes, but we show that weak aggregate approaches do not capture disease state sufficiently, potentially leading to loss of information about response to intervention. We demonstrate how multivariate disease state can be captured using geometric concepts of spaces defined over routine clinical instruments, and show how clinically meaningful disease states (e.g. representing different profiles of symptoms, recovery or remission) can be defined as prototypes (geometric locations) in these spaces. Then, we show how to derive univariate (scalar) measures, which capture patient's relationships to these prototypes and argue these represent strong aggregates of disease state that may be a better basis for outcome measures. We demonstrate our proposal using a large publically available dataset. We conclude by discussing the impact of strong aggregates for analyses in traditional and novel trial designs.</p

Outcomes in treatment-resistant schizophrenia: symptoms, function and clozapine plasma concentrations

Background: Clozapine is the only medication licenced for treating patients with treatment-refractory schizophrenia. However, there are no evidence-based guidelines as to the optimal plasma level of clozapine to aim for, and their association with clinical and functional outcome. Objective: We assessed the relationship between clinical and functional outcome measures and blood concentrations of clozapine among patients with treatment-refractory psychosis. Methods: Data were reviewed in 82 patients with treatment-refractory psychosis admitted to a specialised tertiary-level service and treated with clozapine. Analysis focussed on the relationship between clozapine and norclozapine plasma concentrations and the patient’s clinical symptoms and functional status. Results: Clinical symptom improvement was positively correlated with norclozapine plasma concentrations and inversely correlated with clozapine to norclozapine plasma concentrations ratio. Clozapine concentrations showed a bimodal association with clinical improvement (peaks around 350 and 660 ng/ml). Clinical symptom improvement correlated with functional outcomes, although there was no significant correlation between the latter and clozapine or norclozapine plasma concentrations. Conclusion: Clozapine treatment was associated with optimal clinical improvement at two different peak plasma concentrations around 350 and 650 ng/ml. Clinical improvement was associated with functional outcome; however, functionality was not directly associated with clozapine concentrations. A subset of patients may require higher clozapine plasma concentrations to achieve clinical improvement