Volumetric reductions in the subgenual anterior cingulate cortex in adolescents with bipolar I disorder

Singh MK, Chang KD, Chen MC, Kelley RG, Garrett A, Mitsunaga MM, Bararpour L, Howe M, Reiss AL, Gotlib IH. Volumetric reductions in the subgenual anterior cingulate cortex in adolescents with bipolar I disorder.
Bipolar Disord 2012: 14: 585–596. © 2012 The Authors.
Journal compilation © 2012 John Wiley & Sons A/S. Objectives: A range of prefrontal and subcortical volumetric abnormalities have been found in adults and adolescents with bipolar disorder. It is unclear, however, if these deficits are present early in the onset of mania or are a consequence of multiple mood episodes or prolonged exposure to medication. The goal of this study was to examine whether youth with bipolar I disorder who recently experienced their first episode of mania are characterized by brain volumetric abnormalities. Methods: Anatomical images from magnetic resonance imaging of 26 13‐ to 18‐year‐old adolescents with bipolar I disorder and 24 age‐comparable healthy controls with no personal or family history of psychopathology were analyzed using whole‐brain voxel‐based morphometry (VBM). Results: Compared with healthy controls, adolescents with bipolar I disorder had significantly less gray matter volume in the left subgenual cingulate cortex [p < 0.05, family‐wise error (FWE)‐corrected]. Conclusions: Adolescents with a recent single episode of mania have smaller subgenual cingulate cortex volume than do their healthy counterparts, suggesting that this anomaly occurs early in the onset of, or may predate the disorder. Longitudinal studies are needed to examine the impact of this volumetric reduction on the course and outcome of this disorder.     

Treatment With JAK Inhibitors in Myelofibrosis Patients Nullifies the Prognostic Impact of Unfavorable Cytogenetics

Introduction

In the era before Janus kinase (JAK) inhibitors, cytogenetic information was used to predict survival in myelofibrosis patients. However, the prognostic value of cytogenetics in the setting of JAK inhibitor therapy remains unknown.

Investigation of the copolymerization of mono- and bifunctional monomers of methacrylic esters

The relationships of free-radical copolymerization of mono- and bifunctional monomers were investigated taking as an example a model system of monomers: methyl methacrylate (MMA) and 9,10-dianthrylenedimethyl dimethacrylate ( 1 ). The copolymerization was carried out in toluene at 60°C at a 525: 1 mole ratio of MMA to 1 , with AIBN as initiator. Chemical and luminescent methods for the quantitative determination of bridge bonds containing anthracene moieties in the polymer system and the method of their selective cleavage were developed. Experimental dependences of the concentration of monomers and single and double bonded monomeric units of 1 in the copolymers on the copolymerization time were established. It was found that during the copolymerization the activity of each monomer double bond and that of the pendent double bonds in the monomeric units of 1 in the copolymer are similar. It was shown that over a specific range of changes in the content of bridge bonds (the position of which depends on the length of the chains being crosslinked) the values of the intrinsic viscosity of the copolymer solutions increase cooperatively and gel fraction is formed subsequently.     

Gene expression and pathway analysis of immune thrombocytopenic purpura

A global expression profile of peripheral blood from patients with immune thrombocytopenic purpura (ITP) was performed that identified an ITP-specific signature, which also included interferon (IFN)-induced genes. Several genes correlated with ITP have been shown to be associated with expression signatures in systemic lupus erythematosis and rheumatoid arthritis, indicating an overlap with other autoimmune disorders. Pathway analysis demonstrated that IFN signalling, death receptor and protein ubiquitination pathways were associated with ITP. These results provide the first glimpse of the genes and pathways consistently aberrant in ITP, identifying new targets for investigations of pathogenesis and treatment of ITP.     

Emerging translational science discoveries,clonal approaches,and treatment trends in chronic myeloproliferative neoplasms

The 60th American Society of Hematology (ASH) held in San Diego in December 2018 was followed by the 13th Post‐ASH chronic myeloproliferative neoplasms (MPNs) workshop on December 4 and 5, 2018. This closed annual workshop, first introduced in 2006 by Goldman and Mughal, was organized in collaboration with Alpine Oncology Foundation and allowed experts in preclinical and clinical research in the chronic MPNs to discuss the current scenario, including relevant presentations at ASH, and address pivotal open questions that impact translational research and clinical management. This review is based on the presentations and deliberations at this workshop, and rather than provide a resume of the proceedings, we have selected some of the important translational science and treatment issues that require clarity. We discuss the experimental and observational evidence to support the intimate interaction between aging, inflammation, and clonal evolution of MPNs, the clinical impact of the unfolding mutational landscape on the emerging targets and treatment of MPNs, new methods to detect clonal heterogeneity, the challenges in managing childhood and adolescent MPN, and reflect on the treatment of systemic mastocytosis (SM) following the licensing of midostaurin.     

Dynamic functional connectivity and individual differences in emotions during social stress

Exposure to acute stress induces multiple emotional responses, each with their own unique temporal dynamics. Dynamic functional connectivity (dFC) measures the temporal variability of network synchrony and captures individual differences in network neurodynamics. This study investigated the relationship between dFC and individual differences in emotions induced by an acute psychosocial stressor. Sixteen healthy adult women underwent fMRI scanning during a social evaluative threat (SET) task, and retrospectively completed questionnaires that assessed individual differences in subjectively experienced positive and negative emotions about stress and stress relief during the task. Group dFC was decomposed with parallel factor analysis (PARAFAC) into 10 components, each with a temporal signature, spatial network of functionally connected regions, and vector of participant loadings that captures individual differences in dFC. Participant loadings of two networks were positively correlated with stress‐related emotions, indicating the existence of networks for positive and negative emotions. The emotion‐related networks involved the ventromedial prefrontal cortex, cingulate cortex, anterior insula, and amygdala, among other distributed brain regions, and time signatures for these emotion‐related networks were uncorrelated. These findings demonstrate that individual differences in stress‐induced positive and negative emotions are each uniquely associated with large‐scale brain networks, and suggest that dFC is a mechanism that generates individual differences in the emotional components of the stress response. Hum Brain Mapp 38:6185–6205, 2017. © 2017 Wiley Periodicals, Inc.     

Behavioral and neural correlates of delay of gratification 40 years later

We examined the neural basis of self-regulation in individuals from a cohort of preschoolers who performed the delay-of-gratification task 4 decades ago. Nearly 60 individuals, now in their mid-forties, were tested on "hot" and "cool" versions of a go/nogo task to assess whether delay of gratification in childhood predicts impulse control abilities and sensitivity to alluring cues (happy faces). Individuals who were less able to delay gratification in preschool and consistently showed low self-control abilities in their twenties and thirties performed more poorly than did high delayers when having to suppress a response to a happy face but not to a neutral or fearful face. This finding suggests that sensitivity to environmental hot cues plays a significant role in individuals' ability to suppress actions toward such stimuli. A subset of these participants (n = 26) underwent functional imaging for the first time to test for biased recruitment of frontostriatal circuitry when required to suppress responses to alluring cues. Whereas the prefrontal cortex differentiated between nogo and go trials to a greater extent in high delayers, the ventral striatum showed exaggerated recruitment in low delayers. Thus, resistance to temptation as measured originally by the delay-of-gratification task is a relatively stable individual difference that predicts reliable biases in frontostriatal circuitries that integrate motivational and control processes.