Impulsivity and its relationship with lisdexamfetamine dimesylate treatment in binge eating disorder

High trait impulsivity is thought to contribute to the sense of loss of control over eating and impulses to binge eat experienced by those with binge eating disorder (BED). Lisdexamfetamine dimesylate (LDX), a drug approved for treatment of moderate to severe BED, has been shown to decrease impulsive features of BED. However, the relationship between LDX-related reductions of binge eating (BE) episodes and impulsivity has not yet been explored. Forty-one adults aged 18-40years with moderate to severe BED completed questionnaires and tasks assessing impulsivity at baseline and after 8weeks of 50-70mg of LDX. Twenty age-matched healthy controls were also assessed at two timepoints for normative comparison. Data were analysed using linear mixed models. BED participants exhibited increased self-reported motor, non-planning, cognitive and food-related impulsivity relative to controls but no differences in objective task-based measures of impulsivity. Food-related and non-planning impulsivity was significantly reduced by LDX, but not to normative levels. Individuals with higher baseline levels of motor and non-planning impulsivity, and loss of control over eating scores experienced the greatest reduction in BE frequency after 8weeks of LDX. Further, there were significant associations between the degree to which subjective loss of control over eating, non-planning impulsivity and BE frequency reduced after 8weeks of LDX. These data suggest that specific subjective measures of impulsivity may be able to predict who will have the greatest benefit from LDX treatment and that reductions in BE frequency may be moderated by concurrent reductions in non-planning impulsivity

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

The effect of psychiatric disorders on causal awareness in goal-directed action selection

The ability to calculate the causal efficacy of one’s actions in achieving specific goals is critical for adaptive decision-making. Impaired decision-making is a core feature in many psychiatric disorders, therefore gaining a better understanding of the neural circuits involved in this process may offer insights into phenotypes and more targeted interventions. Here, a free operant probabilistic choice task developed to assess causal awareness in a choice situation was combined with a range of imaging techniques and analytic approaches. The general aim of this thesis was to investigate the role of causal awareness in psychiatric disorders from an associative learning perspective. It was demonstrated that structural differences in the globus pallidus externa are associated with diminished causal awareness in youth with depression, potentially due to an imbalance between direct and indirect basal ganglia circuitry. Further analyses however showed that diminished causal awareness had differing neural aetiologies across differing major psychiatric diagnoses and stages of illness. Nevertheless, it proved to be a cross-diagnostic impairment that was associated with social and functional outcomes. A direct comparison of youth with unipolar depression (UD) and bipolar disorder (BD) revealed similarly suboptimal choices, but due to differing underlying causes; reduced learning rate was an issue in UD, while vacillation was problematic in BD. Finally, in BD, vacillation between choices was associated with increased cognitive instability, possibly related to inhibitory deficits. Attenuated activity in the parietal regions and the dlPFC during exploitation of reward was associated with reduced causal awareness. Early identification of these problems in youth with psychiatric disorders may provide impetus for targeted cognitive interventions, which could be key to reducing the severity and burden of illness or possibly even delaying the development of full threshold disorders

Grey matter abnormalities in children and adolescents with functional neurological symptom disorder

Objective: Functional neurological symptom disorder refers to the presence of neurological symptoms not explained by neurological disease. Although this disorder is presumed to reflect abnormal function of the brain, recent studies in adults show neuroanatomical abnormalities in brain structure. These structural brain abnormalities have been presumed to reflect long-term adaptations to the disorder, and it is unknown whether child and adolescent patients, with illness that is typically of shorter duration, show similar deficits or have normal brain structure. Method: High-resolution, three-dimensional T1-weighted magnetic resonance images (MRIs) were acquired in 25 patients (aged 10–18years) and 24 healthy controls. Structure was quantified in terms of grey matter volume using voxel-based morphometry. Post hoc, we examined whether regions of structural difference related to a measure of motor readiness to emotional signals and to clinical measures of illness duration, illness severity, and anxiety/depression. Results: Patients showed greater volumes in the left supplementary motor area (SMA) and right superior temporal gyrus (STG) and dorsomedial prefrontal cortex (DMPFC) (corrected p<0.05). Previous studies of adult patients have also reported alterations of the SMA. Greater SMA volumes correlated with faster reaction times in identifying emotions but not with clinical measures. Conclusions: The SMA, STG, and DMPFC are known to be involved in the perception of emotion and the modulation of motor responses. These larger volumes may reflect the early expression of an experience-dependent plasticity process associated with increased vigilance to others' emotional states and enhanced motor readiness to organize self-protectively in the context of the long-standing relational stress that is characteristic of this disorder. Keywords: Functional neurological symptom disorder, Conversion disorder, Brain volume, MRI, Psychogenic non-epileptic seizure

Regional brain network organization distinguishes the combined and inattentive subtypes of Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder (ADHD) is characterized clinically by hyperactive/impulsive and/or inattentive symptoms which determine diagnostic subtypes as Predominantly Hyperactive-Impulsive (ADHD-HI), Predominantly Inattentive (ADHD-I), and Combined (ADHD-C). Neuroanatomically though we do not yet know if these clinical subtypes reflect distinct aberrations in underlying brain organization.We imaged 34 ADHD participants defined using DSM-IV criteria as ADHD-I (n=16) or as ADHD-C (n=18) and 28 matched typically developing controls, aged 8–17years, using high-resolution T1 MRI. To quantify neuroanatomical organization we used graph theoretical analysis to assess properties of structural covariance between ADHD subtypes and controls (global network measures: path length, clustering coefficient, and regional network measures: nodal degree). As a context for interpreting network organization differences, we also quantified gray matter volume using voxel-based morphometry.Each ADHD subtype was distinguished by a different organizational profile of the degree to which specific regions were anatomically connected with other regions (i.e., in “nodal degree”). For ADHD-I (compared to both ADHD-C and controls) the nodal degree was higher in the hippocampus. ADHD-I also had a higher nodal degree in the supramarginal gyrus, calcarine sulcus, and superior occipital cortex compared to ADHD-C and in the amygdala compared to controls. By contrast, the nodal degree was higher in the cerebellum for ADHD-C compared to ADHD-I and in the anterior cingulate, middle frontal gyrus and putamen compared to controls. ADHD-C also had reduced nodal degree in the rolandic operculum and middle temporal pole compared to controls. These regional profiles were observed in the context of no differences in gray matter volume or global network organization.Our results suggest that the clinical distinction between the Inattentive and Combined subtypes of ADHD may also be reflected in distinct aberrations in underlying brain organization. Keywords: ADHD, Predominantly inattentive type, Combined type, Structural connectome, Volume, Graph theor