Placebo effect research over the past 15 years has improved our understanding of how placebo treatments reduce patient symptoms. The expectation of symptom improvement is the primary factor underlying the placebo effect. Such expectations are shaped by past experiences, contextual cues and biological traits, which ultimately modulate one's degree of response to a placebo. The body of evidence that describes the physiology of the placebo effect has been derived from mechanistic studies primarily restricted to the setting of pain. Imaging findings support the role of endogenous opioid and dopaminergic networks in placebo analgesia in both healthy patients as well as patients with painful medical conditions. In patients with psychiatric illnesses such as anxiety disorders or depression, a vast overlap in neurological changes is observed in drug responders and placebo responders supporting the role of serotonergic networks in placebo response. Molecular techniques have been relatively underutilized in understanding the placebo effect until recently. We present an overview of the placebo responder phenotypes and genetic markers that have been associated with the placebo effect in pain, schizophrenia, anxiety disorders and depression.

BACKGROUND AND PURPOSE Myelin water imaging (MWI) and diffusion tensor imaging (DTI) provide information about myelin and axon‐related brain microstructure, which can be useful for investigating normal brain development and many childhood brain disorders. While pediatric DTI atlases exist, there are no pediatric MWI atlases available for the 9‐10 years old age group. As myelination and structural development occurs throughout childhood and adolescence, studies of pediatric brain pathologies must use age‐specific MWI and DTI healthy control data. We created atlases of myelin water fraction (MWF) and DTI metrics for healthy children aged 9‐10 years for use as normative data in pediatric neuroimaging studies. METHODS 3D‐T1, DTI, and MWI scans were acquired from 20 healthy children (mean age: 9.6 years, range: 9.2‐10.3 years, 4 females). ANTs and FSL registration were used to create quantitative MWF and DTI atlases. Region of interest (ROI) analysis in nine white matter regions was used to compare pediatric MWF with adult MWF values from a recent study and to investigate the correlation between pediatric MWF and DTI metrics. RESULTS Adults had significantly higher MWF than the pediatric cohort in seven of the nine white matter ROIs, but not in the genu of the corpus callosum or the cingulum. In the pediatric data, MWF correlated significantly with mean diffusivity, but not with axial diffusivity, radial diffusivity, or fractional anisotropy. CONCLUSIONS Normative MWF and DTI metrics from a group of 9‐10 year old healthy children provide a resource for comparison to pathologies. The age‐specific atlases are ready for use in pediatric neuroimaging research and can be accessed: https://sourceforge.net/projects/pediatric-mri-myelin-diffusion/.

Background and Purpose While diffusely abnormal white matter (DAWM) is a nonlesional MRI abnormality identified in ∼25% of patients with multiple sclerosis (MS), it has yet to be investigated in patients at an earlier disease stage, namely clinically isolated syndrome (CIS). The goals of this study were to (1) determine the prevalence of DAWM in patients with a CIS suggestive of MS, (2) evaluate the association between DAWM and demographic, clinical, and MRI features, and (3) evaluate the prognostic significance of DAWM on conversion from CIS to MS. Methods One hundred and forty‐two CIS participants were categorized into DAWM and non‐DAWM groups at baseline and followed for up to 24 months or until MS diagnosis. The primary outcome was conversion to MS (2005 McDonald criteria) within 6 months. Results DAWM was present in 27.5% of participants, and was positively associated with brainstem symptom onset, receiving corticosteroids, dissemination in space, and T2 lesion volume. DAWM was associated with an increased risk of conversion to MS over 6 months after adjustment for age and disability (hazard ratio [HR] = 2.24, p = 0.004). This association remained at a trend‐level after adjustment for high‐risk imaging features (HR = 1.68, p = 0.10). Conclusions DAWM is present in a similar proportion of patients with CIS and clinically definite MS, and it is associated with increased risk of conversion to MS over 6 months.

for his assistance with statistical analysis approaches for the study.Contributors RS, RDH, JS and TL designed and conducted the quality improvement project and performed the intervention. RS and RDH conducted data acquisition. RS, RDH and CN performed data analysis, data interpretation and manuscript preparation, with important intellectual input from TL and JS. All authors approve of the final version of this manuscript.

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