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Introduction: Registration to a standardized template (i.e. "normalization") is a critical step when performing neuroimaging studies. We present a comparative study involving the evaluation of general-purpose registration algorithms for pediatric patients with shunt treated hydrocephalus. Our sample dataset presents a number of intersecting challenges for registration, representing the potentially large deformations to both brain structures and overall brain shape, artifacts from shunts, and morphological differences corresponding to age. The current study assesses the normalization accuracy of shunt-treated hydrocephalus patients using freely available neuroimaging registration tools. Methods: Anatomical neuroimages from eight pediatric patients with shunttreated hydrocephalus were normalized. Four non-linear registration algorithms were assessed in addition to the preprocessing steps of skull-stripping and biascorrection. Registration accuracy was assessed using the Dice Coefficient (DC) and Hausdorff Distance (HD) in subcortical and cortical regions. Results: A total of 592 registrations were performed. On average, normalizations performed using the brain extracted and bias-corrected images had a higher DC and lower HD compared to full head/non-biased corrected images. The most accurate registration was achieved using SyN by ANTs with skull-stripped and bias corrected images. Without preprocessing, the DARTEL Toolbox was able to produce normalized images with comparable accuracy. The use of a pediatric template as an intermediate registration did not improve normalization. Discussion: Using structural neuroimages from patients with shunt-treated pediatric hydrocephalus, it was demonstrated that there are tools which perform well after specified pre-processing steps were taken. Overall, these results provide insight to the performance of registration programs that can be used for normalization of brains with complex pathologies. [ABSTRACT FROM AUTHOR]

Aim: To compare the neurodevelopment of children with unilateral cerebral palsy (CP) with middle cerebral artery (MCA) and periventricular venous infarctions (PVIs). Method: In this cross‐sectional study, children with unilateral CP completed a neurological exam, unimanual Quality of Upper Extremity Skills Test, hand usage questionnaires, and IQ test. Neuroimaging was obtained from health records. Results: Two hundred and forty‐five participants with unilateral CP had neuroimaging (151 [61.9%] male, ages 2–18y, median=7y 6mo, interquartile range [IQR]=6y 7mo, with 93.6% in Gross Motor Function Classification System level I/II and 78.8% in Manual Ability Classification System level I/II). Ninety‐seven (39.6%) had MCA injuries and 106 (43.3%) had periventricular white matter injuries, of which 48 (45.3%) were PVIs. Median Quality of Upper Extremity Skills Test for the MCA group was 49.2 (IQR=55.8), PVI 79.9 (IQR=23.6) (Mann–Whitney U=988.50, p<0.001). Bimanual hand usage (Children's Hand‐use Experience Questionnaire) (Mann–Whitney U=425, p<0.001) and light touch (odds ratio=9.12, 95% confidence interval 1.28–400.76, Fisher's exact test p=0.017) were lower in the MCA compared to the PVI group. Full‐scale IQ median centile score for the MCA group was 18.0 (IQR=35.5) and 50.0 (IQR=30.0) for the PVI group (Mann–Whitney U=382, p<0.001). Interpretation: Children with unilateral CP and MCA injuries demonstrated lower hand function and usage, decreased light touch, and lower IQs compared to the PVI group. This study aids in defining rehabilitation needs informed by brain injury patterns. Video Podcast: https://youtu.be/79w_s82qhr0 [ABSTRACT FROM AUTHOR]

Aim: We sought to compare alterations in serum bioenergetic markers within a well‐characterized sample of adults with schizophrenia at baseline and after 8 weeks of pharmacological treatment with the hypothesis that treatment would be associated with significant changes in bioenergetic markers given the role of bioenergetic dysfunction in schizophrenia. Methods: We recruited adults with schizophrenia (n = 122) who had not received pharmacological treatment for at least 1 month prior to enrollment, including drug‐naïve (i.e., first‐episode) participants and treatment non‐adherent participants. Pre‐ and post‐treatment serum samples were analyzed using liquid chromatography–tandem mass spectrometry. Results: Metabolites with the greatest change, when comparing pre‐ and post‐treatment levels, were identified revealing 14 water‐soluble metabolites of interest. The composition of these metabolites was: amino acids (n = 6), carnitines (n = 4), polar lipids (n = 3), and organic acid (n = 1). All amino acids and lysophosphatidylcholines (LysoPC) were increased, while the four carnitines – oleoylcarnitine, L‐palmitoylcarnitine, linoleyl carnitine, and L‐acetylcarnitine – were decreased post‐treatment. Of these metabolite biomarkers, six – oleoylcarnitine, linoleyl carnitine, L‐acetylcarnitine, LysoPC(15:0), D‐glutamic acid, and L‐arginine – were identified as having most consistently and predictably changed after 8 weeks of treatment. Conclusion: The current study identified several bioenergetic markers that consistently change with pharmacological treatment. These bioenergetic changes may provide further insights into the pathophysiology of schizophrenia along with furthering our understanding of the mechanisms subserving both the effects (e.g., antipsychotic effects) and side‐effects (e.g., metabolic syndrome) of antipsychotics. [ABSTRACT FROM AUTHOR]

Convergent evidence demonstrates that immune dysfunction (e.g. chronic low-grade inflammatory activation) plays an important role in the development and progression of mood disorders. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway is a pleiotropic cellular cascade that transduces numerous signals, including signals from the release of cytokines and growth factors. The JAK/STAT signaling pathway is involved in mediating several functions of the central nervous system, including neurogenesis, synaptic plasticity, gliogenesis, and microglial activation, all of which have been implicated in the pathophysiology of mood disorders. In addition, the antidepressant actions of current treatments have been shown to be mediated by JAK/STAT-dependent mechanisms. To date, two JAK inhibitors (JAKinibs) have been approved by the U.S. Food and Drug Administration and are primarily indicated for the treatment of inflammatory conditions such as rheumatoid arthritis. Indirect evidence from studies in populations with inflammatory conditions indicates that JAKinibs significantly improve measures of mood and quality of life. There is also direct evidence from studies in populations with depressive disorders, suggesting that JAK/STAT pathways may be involved in the pathophysiology of depression and that the inhibition of specific JAK/STAT pathways (i.e. via JAKinibs) may be a promising novel treatment for depressive disorders. [ABSTRACT FROM AUTHOR]

Introduction: To determine, via narrative, non-systematic review of pre-clinical and clinical studies, whether the effect of cannabis on hepatic biotransformation pathways would be predicted to result in clinically significant drug-drug interactions (DDIs) with commonly prescribed psychotropic agents., Areas Covered: A non-systematic literature search was conducted using the following databases: PubMed, PsycInfo, and Scopus from inception to January 2017. The search term cannabis was cross-referenced with the terms drug interactions, cytochrome, cannabinoids, cannabidiol, and medical marijuana. Pharmacological, molecular, and physiologic studies evaluating the pharmacokinetics of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD), both in vitro and in vivo, were included. Bibliographies were also manually searched for additional citations that were relevant to the overarching aim of this paper., Expert Opinion: Δ 9 -Tetrahydrocannabinol and CBD are substrates and inhibitors of cytochrome P450 enzymatic pathways relevant to the biotransformation of commonly prescribed psychotropic agents. The high frequency and increasing use of cannabis invites the need for healthcare providers to familiarize themselves with potential DDIs in persons receiving select psychotropic agents, and additionally consuming medical marijuana and/or recreational marijuana.

Cognitive dysfunction is a major component of major depressive disorder (MDD). No 'gold-standard' tool exists for the assessment of cognitive dysfunction for adults with MDD. The use of measurement-based care to improve treatment outcomes invites the need for a systematic screening, evaluation and measurement tool. The aim herein was to provide a succinct summary of literature documenting clinical implication of cognitive dysfunction in MDD, and a review of available screening, diagnostic and measurement tools for cognitive dysfunction in MDD is provided. We also take the opportunity to introduce a screening tool (ie, the THINC-it tool) targeted at addressing the unmet needs. We found that there are limitations to the current measurement scales; for example, many are not targeted for MDD and not all digitally available tests are free of charge. Furthermore, the spectrum of cognitive dysfunction in MDD is poorly represented by the existing tests and as such, there is a lack of sensitivity in the ability to screen a patient with MDD for a cognitive dysfunction. Recognising and addressing the limitations in the current screening techniques for cognitive dysfunction as well as being presented with the current tools available provides the ability to perform an educated cognitive screening for a patient with MDD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)