Wellbeing differences in children with synaesthesia: anxiety and mood regulation.

Synaesthesia is a neurodevelopmental trait that causes unusual sensory experiences (e.g., perceiving colours when reading letters and numbers). Our paper represents the first evidence that synaesthesia can impact negatively on children's well-being, and that there are likely to be important mental health co-morbidities for children with synaesthesia. We recruited 76 synaesthetes aged 6-10 years who had one of two types of synaesthesia (grapheme-colour synaesthesia and sequence-personality synaesthesia), and compared them to almost one thousand matched non-synaesthete controls. We tested children's wellbeing with two different measures, and found a significant relationship between synaesthesia and affect (i.e., mood), and also between synaesthesia and anxiety. Children with synaesthesia showed evidence suggesting significantly higher rates of Anxiety Disorder, and also displayed a type of mood-moderation in demonstrating fewer extremes of emotion (i.e., significantly fewer negative feelings such as fear, but also significantly fewer positive feelings such as joy). We discuss our results with reference to the emotional moderation of alexithymia (the inability to recognize or describe one's own emotions), and to a set of known links between alexithymia, anxiety, autism and synaesthesia.

Personality profile of child synaesthetes.

Previous research into personality and synaesthesia has focused on adult populations and yielded mixed results. One particular challenge has been to distinguish traits associated with synaesthesia, from traits associated with the ways in which synaesthetes were recruited. In the current study we addressed recruitment issues by testing randomly sampled synaesthetes, and we looked particularly at synaesthesia in childhood. Our child synaesthetes were identified by a screening program across 22 primary schools in the South East of England (n = 3387; children aged 6 to 10 years old). This identified two types of synaesthete (grapheme-colour synaesthesia and sequence-personality synaesthesia), and we tested their personalities using both child-report and parent-report measures. We found strong support for synaesthesia being associated with high Openness to Experience, a personality trait linked to intelligence and creativity. Both synaesthesia subtypes showed this feature, supporting previous research in adults (1-3). We additionally found low Extraversion in grapheme-colour synaesthetes and high Conscientiousness in sequence-personality synaesthetes. We discuss our results with reference to earlier recruitment issues, and as to how perceptual differences such as synaesthesia might link to trait-differences in personality.

Numeracy skills in child synaesthetes: Evidence from grapheme-colour synaesthesia.

Grapheme-colour synaesthesia is a neurological trait that causes lifelong colour associations for letter and numbers. Synaesthesia studies have demonstrated differences between synaesthetes and non-synaesthetes in ways that extend beyond synaesthesia itself (e.g., differences in their cognition, personality, and creativity). This research has focused almost exclusively on adult synaesthetes, and little is known about the profiles of synaesthetic children. By and large, findings suggest advantages for synaesthetes (e.g., Chun & Hupé, 2016; Havlik, Carmichael, & Simner, 2015; Rothen, Meier, & Ward, 2012; Rouw & Scholte, 2016; Simner & Bain, 2018) although differences in mathematical ability are unclear: some research indicates advantages (e.g., Green & Goswami, 2008) whilst others suggest difficulties (e.g., Rich et al., 2005). In the current study, we tested numerical cognition in a large group of children with grapheme-colour synaesthesia. Synaesthetes with coloured numbers showed advantages over their peers in their sense of numerosity, but not in their curriculum mathematics ability. We discuss how our findings speak to models for synaesthesia, to methodologies for assessing number cognition (e.g., dot numerosity tasks), and to the wider educational practice of using coloured number-tools in schools (e.g., Numicon; Oxford University Press, 2018).

Investigating genetic links between grapheme-colour synaesthesia and neuropsychiatric traits.

Synaesthesia is a neurological phenomenon affecting perception, where triggering stimuli (e.g. letters and numbers) elicit unusual secondary sensory experiences (e.g. colours). Family-based studies point to a role for genetic factors in the development of this trait. However, the contributions of common genomic variation to synaesthesia have not yet been investigated. Here, we present the SynGenes cohort, the largest genotyped collection of unrelated people with grapheme-colour synaesthesia (n = 723). Synaesthesia has been associated with a range of other neuropsychological traits, including enhanced memory and mental imagery, as well as greater sensory sensitivity. Motivated by the prior literature on putative trait overlaps, we investigated polygenic scores derived from published genome-wide scans of schizophrenia and autism spectrum disorder (ASD), comparing our SynGenes cohort to 2181 non-synaesthetic controls. We found a very slight association between schizophrenia polygenic scores and synaesthesia (Nagelkerke's R2 = 0.0047, empirical p = 0.0027) and no significant association for scores related to ASD (Nagelkerke's R2 = 0.00092, empirical p = 0.54) or body mass index (R2 = 0.00058, empirical p = 0.60), included as a negative control. As sample sizes for studying common genomic variation continue to increase, genetic investigations of the kind reported here may yield novel insights into the shared biology between synaesthesia and other traits, to complement findings from neuropsychology and brain imaging. This article is part of a discussion meeting issue 'Bridging senses: novel insights from synaesthesia'.

Learning in colour: children with grapheme-colour synaesthesia show cognitive benefits in vocabulary and self-evaluated reading.

Cognitive benefits associated with grapheme-colour synaesthesia in adults are well documented, but far less is known about whether such benefits might arise in synaesthetes as children. One previous study on a very small group of randomly sampled child synaesthetes found cognitive benefits in short-term memory and processing speed (the ability to quickly scan an array of images and discriminate between them), but was inconclusive for a test of receptive vocabulary. Using a stratified population sample (Growing Up in Scotland Project, Edinburgh, UK: Scottish Executive, 2007), we investigated the performance of a large cohort of child grapheme-colour synaesthetes using four literacy measures taken at age 10 years. These were three verbal comprehension measures (expressive vocabulary, receptive vocabulary and sentence comprehension) and one measure of academic self-concept in reading (plus one measure of academic self-concept in numeracy as a comparison). After controlling for demographic differences between groups, synaesthetes showed significantly enhanced performance for expressive and receptive vocabulary compared to their peers, but no benefits in sentence comprehension. Child synaesthetes also reported significantly higher academic self-concept for reading, but not for numeracy. Finally, we found that synaesthetes made significantly more progress than controls across the primary school years, although they began school with no a priori advantage. Our study provides powerful new evidence that children with grapheme-colour synaesthesia show vocabulary and literacy differences, which we contextualize within a theory of synaesthetic development. This article is part of a discussion meeting issue 'Bridging senses: novel insights from synaesthesia'.

Structure of Electronically Reduced N-Donor Bidentate Ligands and Their Heteroleptic Four-Coordinate Zinc Complexes: A Survey of Density Functional Theory Results.

The role of Hartree-Fock exchange in describing the structural changes occurring upon reduction of bipyridine-based ligands and their complexes is investigated within the framework of density functional theory (DFT) calculations. A set of four free ligands in their neutral and radical anionic forms, and two of their zinc complexes in their dicationic and monocationic radical forms, is used to compare a large panel of pure, conventional, and long-range corrected hybrid DFT functionals; coupled cluster single and double calculations are used alongside experimental results as benchmarks. Particular attention has been devoted to the magnitude of the change, upon reduction, of the Δ-parameter, which measures the difference between the Cpy-Cpy and the C-N bond lengths in bipyridine ligand and is known to experimentally correlate with the charge of the ligands. Our results indicate that the structural changes significantly depend on the amount of exact exchange included in the functional. A progressive evolution is observed for the free ligands, whereas two distinct sets of results are obtained for the complexes. Functionals with a small degree of HF exchange, e.g., B3LYP, do not adequately describe geometric changes for the considered species, and, quite surprisingly, the same holds for the CC2 method. The best agreement to experimental and CCSD values is obtained with functionals that include a significant but not excessive part of exact exchange, e.g., CAM-B3LYP, M06-2X, and ωB97X-D. The calculated localization of the added electron after reduction, which depends on the self-interaction error, is used to rationalize these outcomes. Static correlation is also shown to play a role in the accurate description of the electronic structure.

Is there a burden attached to synaesthesia? Health screening of synaesthetes in the general population.

Synaesthesia has long been considered a benign alternative form of perception most often associated with positive rather than negative outcomes. The condition has been associated with a variety of cognitive and perceptual advantages, including benefits in memory, processing speed, and creativity. It is not currently recognized in the DSM-IV. Recently, however, several studies have raised the question of a possible link between synaesthesia and clinical conditions. Here, we present the first large-scale screening of the general population in which we (1) objectively identified grapheme-colour synaesthetes and (2) elicited information from our participants about a range of clinical conditions. We compared the prevalence rates of these conditions in synaesthetes versus non-synaesthetes to establish whether any conditions were found at a higher rate among synaesthetes. In our initial study, screening 3,742 people (95 synaesthetes and 3,647 controls), we found initially that grapheme-colour was significantly comorbid with two conditions (anxiety disorder and obsessive compulsive disorder). In our second study, screening a new population of 120 synaesthetes and 166 non-synaesthetes, we replicated our finding that grapheme-colour synaesthesia is comorbid with anxiety disorder. At the same time, we also addressed a methodological concern that likely elevated rates of OCD in Study 1. We consider the aetiology of synaesthesia to determine whether there may be a shared genetic or neurological basis with anxiety disorder, and we question the status of synaesthesia within a mental health framework.

European guidelines for workplace drug testing in oral fluid.

These guidelines for Legally Defensible Workplace Drug Testing have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing should use these guidelines as a template for accreditation. These guidelines are relevant to laboratory-based testing only. These guidelines follow current best practices and are constantly under review.

Improved Infrared Spectra Prediction by DFT from a New Experimental Database.

This work aims to improve the computation of infrared spectra of gas-phase cations using DFT methods. Experimental infrared multiple photon dissociation (IRMPD) spectra for ten Zn and Ru organometallic complexes have been used to provide reference data for 64 vibrational modes in the 900-2000 cm-1 range. The accuracy of the IR vibrational frequencies predicted for these bands has been assessed over five DFT functionals and three basis sets. The functionals include the popular B3LYP and M06-2X hybrids and the range-separated hybrids (RSH) CAM-B3LYP, LC-BLYP, and ωB97X-D. B3LYP gives the best mean absolute error (MAE) and root-mean-square error (RMSE) values of 7.1 and 9.6 cm-1 , whilst the best RSH functional, ωB97X-D, gives 12.8 and 16.6 cm-1 , respectively. Using linear correlations instead of scaling factors improves the prediction accuracy significantly for all functionals. Experimental and computed spectra for a single complex can show significant differences even when the molecular structure is calculated correctly, and a means of defining confidence limits for any given computed structure is also provided.

European guidelines for workplace drug testing in urine.

These European Guidelines for Workplace Drug Testing in Urine have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). The first version of these urine guidelines was published in 2002. Since then, the guidelines have been followed by many laboratories in different European countries and their role has been essential particularly in countries lacking legislation for workplace drug testing. In 2014, the EWDTS started a guidelines updating project and published a new version of the urine guidelines in 2015. Here we represent this updated version of the urine guidelines. The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing should use these guidelines as a template for accreditation. Copyright © 2017 John Wiley & Sons, Ltd.

Different Dimensions of Cognitive Style in Typical and Atypical Cognition: New Evidence and a New Measurement Tool.

We developed the Sussex Cognitive Styles Questionnaire (SCSQ) to investigate visual and verbal processing preferences and incorporate global/local processing orientations and systemising into a single, comprehensive measure. In Study 1 (N = 1542), factor analysis revealed six reliable subscales to the final 60 item questionnaire: Imagery Ability (relating to the use of visual mental imagery in everyday life); Technical/Spatial (relating to spatial mental imagery, and numerical and technical cognition); Language & Word Forms; Need for Organisation; Global Bias; and Systemising Tendency. Thus, we replicate previous findings that visual and verbal styles are separable, and that types of imagery can be subdivided. We extend previous research by showing that spatial imagery clusters with other abstract cognitive skills, and demonstrate that global/local bias can be separated from systemising. Study 2 validated the Technical/Spatial and Language & Word Forms factors by showing that they affect performance on memory tasks. In Study 3, we validated Imagery Ability, Technical/Spatial, Language & Word Forms, Global Bias, and Systemising Tendency by issuing the SCSQ to a sample of synaesthetes (N = 121) who report atypical cognitive profiles on these subscales. Thus, the SCSQ consolidates research from traditionally disparate areas of cognitive science into a comprehensive cognitive style measure, which can be used in the general population, and special populations.

Combining gas phase electron capture and IRMPD action spectroscopy to probe the electronic structure of a metastable reduced organometallic complex containing a non-innocent ligand.

Combining electron capture dissociation mass spectrometry and infrared multiple photon dissociation action spectroscopy allows the formation, selection and characterisation of reduced metal complexes containing non-innocent ligands. Zinc complexes containing diazafluorenone ligands have been studied and the localisation of the single electron on the metal atom in the mono-ligated complex has been demonstrated.

Do sequence-space synaesthetes have better spatial imagery skills? Yes, but there are individual differences.

People with sequence-space synaesthesia perceive sequences (e.g. numbers, months, letters) as spatially extended forms. Here, we ask whether sequence-space synaesthetes have advantages in visuo-spatial skills such as mental rotation. Previous studies addressing this question have produced mixed results with some showing mental rotation advantages (Simner et al. in Cortex 45:1246-1260, 2009; Brang et al. in Cogn Process, 2013), but one that did not (Rizza and Price in Cogn Process 13:299-303, 2012). We tested this hypothesis again with a new group of sequence-space synaesthetes, and we also tested a range of individual differences that might have caused this conflict across previous studies. Specifically, we tested: years of education, visual imagery ability, nature of forms (2D or 3D representation of sequences), number of forms (e.g. for months, days, numbers), and tendency to project sequences into external space versus the mind's eye. We found yet again that synaesthetes had enhanced abilities in mental rotation compared to controls, but that one individual difference in synaesthetes (the ability to project forms into space) was especially linked to performance. We also found that synaesthetes self-reported higher visual imagery than controls (Price in Cortex 45:1229-1245, 2009; Mann et al. in Conscious Cognit 18:619-627, 2009; Rizza and Price 2012). Overall, our data support previous studies showing superior imagery reports (Price 2009) and mental rotation (Simner et al. 2009; Brang et al. 2013) in sequence-space synaesthetes, and we suggest that one previous failure to replicate (Rizza and Price 2012) might be explained by individual differences among synaesthetes recruited for testing.

Exploiting the Brønsted acidity of phosphinecarboxamides for the synthesis of new phosphides and phosphines.

We demonstrate that the synthesis of new N-functionalized phosphinecarboxamides is possible by reaction of primary and secondary amines with PCO(-) in the presence of a proton source. These reactions proceed with varying degrees of success, and although primary amines generally afford the corresponding phosphinecarboxamides in good yields, secondary amines react more sluggishly and often give rise to significant decomposition of the 2-phosphaethynolate precursor. Of the new N-derivatized phosphinecarboxamides available, PH2C(O)NHCy (Cy = cyclohexyl) can be obtained in sufficiently high yields to allow for the exploration of its Brønsted acidity. Thus, deprotonating PH2C(O)NHCy with one equivalent of potassium bis(trimethylsilyl)amide (KHMDS) gave the new phosphide [PHC(O)NHCy](-). In contrast, deprotonation with half of an equivalent gives rise to [P{C(O)NHCy}2](-) and PH3. These phosphides can be employed to give new phosphines by reactions with electrophiles, thus demonstrating their enormous potential as chemical building blocks.

Is synaesthesia a dominantly female trait?

Synaesthesia is a familial condition that gives rise to unusual secondary percepts. We present a large-scale prevalence study which informs our ideas on whether the condition is more prevalent in men or women. A number of studies over the last 20 years have suggested the condition is found more commonly in women, with up to six times more female synaesthetes than male. Other studies attributed this female bias to merely a recruitment confound: women synaesthetes may be more likely to self-refer for study. We offer two pieces of evidence that there is no extreme female bias in synaesthesia: first we re-analyse previous reports of very large female biases to show again that they likely arose from self-referral or other methodological issues. Second, we present the largest published prevalence study to date on grapheme→colour synaesthesia in which our prevalence (1.39% of the population) replicates our earlier estimates (and in which we demonstrate no strong female bias even with sufficient power to detect such a difference.

Colour fluctuations in grapheme-colour synaesthesia: The effect of clinical and non-clinical mood changes.

Synaesthesia is a condition that gives rise to unusual secondary sensations (e.g., colours are perceived when listening to music). These unusual sensations tend to be reported as being stable throughout adulthood (e.g., Simner & Logie, 2007, Neurocase, 13, 358) and the consistency of these experiences over time is taken as the behavioural hallmark of genuineness. Our study looked at the influence of mood states on synaesthetic colours. In Experiment 1, we recruited grapheme-colour synaesthetes (who experience colours from letters/digits) and elicited their synaesthetic colours, as well as their mood and depression states, in two different testing sessions. In each session, participants completed the PANAS-X (Watson & Clark, 1999) and the BDI-II (Beck, Steer, & Brown, 1996, Manual for Beck Depression Inventory-II), and chose their synaesthetic colours for letters A-Z from an interactive colour palette. We found that negative mood significantly decreased the luminance of synaesthetic colours. In Experiment 2, we showed that synaesthetic colours were also less luminant for synaesthetes with anxiety disorder, versus those without. Additional evidence suggests that colour saturation, too, may inversely correlate with depressive symptoms. These results show that fluctuations in mood within both a normal and clinical range influence synaesthetic colours over time. This has implications for our understanding about the longitudinal stability of synaesthetic experiences, and of how mood may interact with the visual (imagery) systems.

Rates of white matter hyperintensities compatible with the radiological profile of multiple sclerosis within self-referred synesthete populations.

Synesthesia is an inherited condition causing unusual secondary sensations (e.g, sounds might be experienced as both auditory and visual percepts). The condition has been linked with cognitive and perceptual benefits and is considered a benign alternative form of perception. Here, we investigate self-referred synesthete populations and their rates of radiologically determined white matter hyperintensities (WMH) of a type compatible with the McDonald imaging criteria for the diagnosis of multiple sclerosis (MS). MS is a chronic condition resulting in damage to myelination surrounding nerve fibers of the central nervous system (CNS). Magnetic resonance imaging (MRI) features highly suggestive of MS without overt clinical symptoms are termed radiologically isolated syndrome (RIS). We present data showing that the shared MRI profile of MS and RIS has been significantly overrepresented in synesthetes who have participated in neuroimaging research. We present validation of the clinical and MRI status of these synesthetes and an analysis showing the significant probability their unusual numbers may not have arisen by chance. We discuss how to interpret significant data based on small case numbers and consider the implications of our findings for synesthesia's clinical status.

Easy and quantitative access to Fe(II) and Fe(III) di(aryl)alkynylphosphine oxides featuring [Fe(dppe)Cp*] endgroups: terminal P=O functionality blocks the dimerisation of the Fe(III) derivatives.

A series of paramagnetic di(aryl)alkynylphosphine oxides [PF6] featuring an open-shell [Fe(κ(2)-dppe)(η(5)-C5Me5)](+) endgroup were obtained by oxidation of their neutral Fe(II) parents 3a-c, themselves obtained in a simple and nearly quantitative fashion from the corresponding Fe(II) metallophosphines 1a-c. The new organometallic radicals were characterised by NMR and ESR and were shown to be perfectly stable in solution, in contrast to species such as 1a-b[PF6] which readily dimerise.