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Becky Inkster

Bio: Becky Inkster is an academic researcher from University of Cambridge. The author has contributed to research in topics: Mental health & Erythropoietin. The author has an hindex of 21, co-authored 42 publications receiving 2010 citations. Previous affiliations of Becky Inkster include National Health Service & Imperial College London.

Papers
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Journal ArticleDOI
TL;DR: The reliability, short acquisition time, high resolution and the detailed insights into the brain microstructure provided by MPM makes it an efficient tool for multi-center imaging studies.
Abstract: Multi-center studies using magnetic resonance imaging facilitate studying small effect sizes, global population variance and rare diseases. The reliability and sensitivity of these multi-center studies crucially depend on the comparability of the data generated at different sites and time points. The level of inter-site comparability is still controversial for conventional anatomical T1-weighted MRI data. Quantitative multi-parameter mapping (MPM) was designed to provide MR parameter measures that are comparable across sites and time points, i.e., 1mm high-resolution maps of the longitudinal relaxation rate (R1=1/T1), effective proton density (PD*), magnetization transfer saturation (MT) and effective transverse relaxation rate (R2*=1/T2*). MPM was validated at 3T for use in multi-center studies by scanning five volunteers at three different sites. We determined the inter-site bias, inter-site and intra-site coefficient of variation (CoV) for typical morphometric measures (i.e., gray matter probability maps used in voxel-based morphometry) and the four quantitative parameters. The inter-site bias and CoV were smaller than 3.1% and 8%, respectively, except for the inter-site CoV of R2* (< 20%). The gray matter probability maps based on the MT parameter maps had a 14% higher inter-site reproducibility than maps based on conventional T1-weighted images. The low inter-site bias and variance in the parameters and derived gray matter probability maps confirm the high comparability of the quantitative maps across sites and time points. The reliability, short acquisition time, high resolution and the detailed insights into the brain microstructure provided by MPM makes it an efficient tool for multi-center imaging studies.

452 citations

Journal ArticleDOI
TL;DR: It is concluded that normative human brain maturation involves a genetically patterned process of consolidating anatomical network hubs and developmental variation of this consolidation process may be relevant both to normal cognitive and behavioral changes and the high incidence of schizophrenia during human brain adolescence.
Abstract: How does human brain structure mature during adolescence? We used MRI to measure cortical thickness and intracortical myelination in 297 population volunteers aged 14-24 y old. We found and replicated that association cortical areas were thicker and less myelinated than primary cortical areas at 14 y. However, association cortex had faster rates of shrinkage and myelination over the course of adolescence. Age-related increases in cortical myelination were maximized approximately at the internal layer of projection neurons. Adolescent cortical myelination and shrinkage were coupled and specifically associated with a dorsoventrally patterned gene expression profile enriched for synaptic, oligodendroglial- and schizophrenia-related genes. Topologically efficient and biologically expensive hubs of the brain anatomical network had greater rates of shrinkage/myelination and were associated with overexpression of the same transcriptional profile as cortical consolidation. We conclude that normative human brain maturation involves a genetically patterned process of consolidating anatomical network hubs. We argue that developmental variation of this consolidation process may be relevant both to normal cognitive and behavioral changes and the high incidence of schizophrenia during human brain adolescence.

401 citations

Journal ArticleDOI
TL;DR: Evidence from genetics, molecular neurobiology, systems neuroscience, and systems neuroscience relating to the role of GABA in autism spectrum disorders is reviewed, discussing how deficits may relate to the specific symptoms observed.

348 citations

Journal ArticleDOI
TL;DR: A preliminary real-world data evaluation of the effectiveness and engagement levels of an AI-enabled, empathetic, text-based conversational mobile mental well-being app, Wysa, on users with self-reported symptoms of depression shows promise.
Abstract: Background: A World Health Organization 2017 report stated that major depression affects almost 5% of the human population. Major depression is associated with impaired psychosocial functioning and reduced quality of life. Challenges such as shortage of mental health personnel, long waiting times, perceived stigma, and lower government spends pose barriers to the alleviation of mental health problems. Face-to-face psychotherapy alone provides only point-in-time support and cannot scale quickly enough to address this growing global public health challenge. Artificial intelligence (AI)-enabled, empathetic, and evidence-driven conversational mobile app technologies could play an active role in filling this gap by increasing adoption and enabling reach. Although such a technology can help manage these barriers, they should never replace time with a health care professional for more severe mental health problems. However, app technologies could act as a supplementary or intermediate support system. Mobile mental well-being apps need to uphold privacy and foster both short- and long-term positive outcomes. Objective: This study aimed to present a preliminary real-world data evaluation of the effectiveness and engagement levels of an AI-enabled, empathetic, text-based conversational mobile mental well-being app, Wysa, on users with self-reported symptoms of depression. Methods: In the study, a group of anonymous global users were observed who voluntarily installed the Wysa app, engaged in text-based messaging, and self-reported symptoms of depression using the Patient Health Questionnaire-9. On the basis of the extent of app usage on and between 2 consecutive screening time points, 2 distinct groups of users (high users and low users) emerged. The study used mixed-methods approach to evaluate the impact and engagement levels among these users. The quantitative analysis measured the app impact by comparing the average improvement in symptoms of depression between high and low users. The qualitative analysis measured the app engagement and experience by analyzing in-app user feedback and evaluated the performance of a machine learning classifier to detect user objections during conversations. Results: The average mood improvement (ie, difference in pre- and post-self-reported depression scores) between the groups (ie, high vs low users; n=108 and n=21, respectively) revealed that the high users group had significantly higher average improvement (mean 5.84 [SD 6.66]) compared with the low users group (mean 3.52 [SD 6.15]); Mann-Whitney P=.03 and with a moderate effect size of 0.63. Moreover, 67.7% of user-provided feedback responses found the app experience helpful and encouraging. Conclusions: The real-world data evaluation findings on the effectiveness and engagement levels of Wysa app on users with self-reported symptoms of depression show promise. However, further work is required to validate these initial findings in much larger samples and across longer periods.

327 citations

Journal ArticleDOI
TL;DR: The association of GSK3beta polymorphisms with structural variation in the temporal lobe and hippocampus is of particular interest in the context of other evidence for structural and functional abnormalities in the hippocampi of patients with MDD.
Abstract: Context: Indirect evidence suggests that the glycogen synthase kinase-3β (GSK3β) gene might be implicated in major depressive disorder (MDD). Background: We evaluated 15 GSK3β single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients with recurrent MDD. We then used the defined regions of interest based on significant associations to test for MDD x genotype interactions by including a matched control group without any psychiatric disorder, including MDD. Design: General linear model with nonstationary cluster-based inference. Setting: Munich, Germany. Participants: Patients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143). Main Outcome Measures: Associations between GSK3β polymorphisms and regional GM volume differences. Results: Variation in GM volume was associated with GSK3β polymorphisms; the most significant associations were found for rs6438552, a putative functional intronic SNP that showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). Similar results were obtained with rs12630592, an SNP in high linkage disequilibrium. A significant SNP x MDD status interaction was observed for the effect on GM volumes in the right hippocampus and superior temporal gyri (P < .001 and P = .01, corrected, respectively). Conclusions: The GSK3β gene may have a role in determining regional GM volume differences of the right hippocampus and bilateral superior temporal gyri. The association between genotype and brain structure was specific to the patients with MDD, suggesting that GSK3β genotypes might interact with MDD status. We speculate that this is a consequence of regional neocortical, glial, or neuronal growth or survival. In considering core cognitive features of MDD, the association of GSK3β polymorphisms with structural variation in the temporal lobe and hippocampus is of particular interest in the context of other evidence for structural and functional abnormalities in the hippocampi of patients with MDD.

116 citations


Cited by
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TL;DR: Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD, and seven genes for which the same variant has been studied in three or more case-control or family-based studies show statistically significant evidence of association with ADHD.

2,087 citations

Journal Article
TL;DR: This study has detailed neurofunctional maps to use as normative references in future fMRI studies of emotional facial processing in psychiatric populations, and found selective differences between neural networks underlying the basic emotions in limbic and insular brain regions.
Abstract: ies using a variant of the emotional faces paradigm in healthy participants. The search terms were: “fMRI AND happy faces,” “fMRI AND sad faces,” “fMRI AND fearful faces,” “fMRI AND angry faces,” “fMRI AND disgusted faces” and “fMRI AND neutral faces.” We extracted spatial coordinates and inserted them in an electronic database. We performed activation likelihood estimation analysis for voxel-based meta-analyses. Results: Of the originally identified studies, 105 met our inclusion criteria. The overall database consisted of 1785 brain coordinates that yielded an overall sample of 1600 healthy participants. Quantitative voxel-based meta-analysis of brain activation provided neurofunctional maps for 1) main effect of human faces; 2) main effect of emotional valence; and 3) modulatory effect of age, sex, explicit versus implicit processing and magnetic field strength. Processing of emotional faces was associated with increased activation in a number of visual, limbic, temporoparietal and prefrontal areas; the putamen; and the cerebellum. Happy, fearful and sad faces specifically activated the amygdala, whereas angry or disgusted faces had no effect on this brain region. Furthermore, amygdala sensitivity was greater for fearful than for happy or sad faces. Insular activation was selectively reported during processing of disgusted and angry faces. However, insular sensitivity was greater for disgusted than for angry faces. Conversely, neural response in the visual cortex and cerebellum was observable across all emotional conditions. Limitations: Although the activation likelihood estimation approach is currently one of the most powerful and reliable meta-analytical methods in neuroimaging research, it is insensitive to effect sizes. Conclusion: Our study has detailed neurofunctional maps to use as normative references in future fMRI studies of emotional facial processing in psychiatric populations. We found selective differences between neural networks underlying the basic emotions in limbic and insular brain regions.

1,283 citations

Journal ArticleDOI
TL;DR: Glycogen synthase kinase-3 (GSK3) must be particularly adaptable for incorporating new substrates into its repertoire, and the distinct properties of GSK3 that may contribute to its capacity to fulfill its roles in multiple signaling pathways are discussed.

1,125 citations

Journal ArticleDOI
TL;DR: Although twin studies demonstrate that ADHD is a highly heritable condition, molecular genetic studies suggest that the genetic architecture of ADHD is complex as discussed by the authors, and the handful of genomewide linkage and association scans that have been conducted thus far show divergent findings and are therefore not conclusive.

973 citations