adenosine triphosphate These findings must be interpreted wi

These findings must be interpreted with limitations in mind. The study was a parallel group, longitudinal design typical for assessing treatment effects. However, the control group were healthy adolescents rather than patients randomized to placebo, due to ethical concerns of withholding treatment and the difficulty of providing a placebo conversational therapy. Therefore, we cannot conclude whether improvements were due to CBT or non-specific effects of improvement in symptoms. Patients were recruited from the IMPACT effectiveness trial with potential participants approached sequentially in clinical settings. The sample thus reflects the local patient population, subject to biases in consenting. Male participants constituted around 25% (25/91), which differs from the 2:1 female:male ratio more widely observed in adolescents with depression (Murray, 2013). Furthermore, the follow-up patient sample was limited in size. The 11–17years age range covers the period during which adenosine triphosphate maturation is significant. As treatment effects were the focus of the study, effects of age and gender, although modelled, were not investigated here. There were no significant demographic differences between groups. Significant between-group differences in some head motion parameters were found. Hence, motion cannot be completely ruled out as a source of between-group rsFC differences. However, in a comparison of a subset of participants with no significant between-group difference in DVARS, patterns of increased rsFC in the limbic system were sustained (Fig. S3). In summary, this study investigated rsFC differences in adolescents with MDD compared to healthy controls. Depressed adolescents demonstrated greater rsFC in limbic regions associated with ‘hot’ emotional processing in the absence of differences in regions associated with ‘cold’ cognition; that is, an imbalance between these systems. This is possibly due to the relative speeds of maturation of the two systems (Hagan et al., 2015). Coupled with similar results from elsewhere, rsFC is a potential marker for MDD in adolescence. Neurobiologically, CBT normalized aberrant rsFC patterns in the limbic system of adolescents with MDD. Symptom recovery may at least in part be associated with a ‘cooling’ of ‘hot’ emotional brain systems, and their restoration is a key component of the mechanism of action of therapeutic interventions, such as CBT.
Funding Sources UK Medical Research Council (MRC) (grant: G0802226), National Institute for Health Research (grant: 06-05-01), the Department of Health, Behavioral and Clinical Neuroscience Institute (University of Cambridge), the latter being jointly funded by the MRC and the Wellcome Trust. Additional support received from the Cambridge Biomedical Research Centre. SC is supported by the University of Cambridge Overseas Trust and CONACyT: Data collection and analyses.
Conflicts of Interests
Author Contributions
Acknowledgements The study was funded by the UK Medical Research Council (grant: G0802226), the National Institute for Health Research (NIHR) (grant: 06-05-01), financial support from the Department of Health, and the Behavioral and Clinical Neuroscience Institute (BCNI), University of Cambridge, the latter being jointly funded by the Medical Research Council and the Wellcome Trust. Additional support was received from the Cambridge Biomedical Research Centre. SC is supported by a Cambridge CONACyT scholarship from the University of Cambridge Overseas Trust and CONACyT.
Introduction Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer by incidence (Siegel et al., 2016), and a leading cause of cancer-related death (Belcher et al., 2014). HNSCC displays substantial variability in prognosis and response to standard therapies (Belcher et al., 2014), which may reflect underlying etiological and molecular heterogeneity. For example, it is now well-understood that HNSCCs caused by high risk strains of human papilloma virus (HPV) are molecularly distinct from HPV negative (HPV−) HNSCCs and that they have better prognosis and therapy response (Wise-Draper et al., 2012; Kimple et al., 2013). Smoking is the major risk factor for HPV− HNSCC, causing genetic mutations in tumor suppressor genes including TP53 (DeMarini, 2004; Vettore et al., 2015). Alcohol consumption is a modest risk factor for HNSCC and is thought to increase risk particularly in smokers (Dal Maso et al., 2016). However, there is an increasingly recognized incidence of HPV− HNSCCs in individuals with no smoking history, indicating that etiological factors other than smoking and HPV exist (Heaton et al., 2014; Harris et al., 2011; Chaturvedi et al., 2013; Toner and O\'Regan, 2009; MacKenzie et al., 2000; Patel et al., 2011; Koch et al., 1999; Koo et al., 2013; Brown et al., 2012; Montero et al., 2012; Perry et al., 2015; Toporcov et al., 2015). HNSCCs lacking these classic risk factors, referred to as ‘atypical’ HNSCCs, are usually oral squamous cell carcinomas (OSCCs), occur with higher relative frequency in women (particularly women of low socioeconomic status (Conway et al., 2008; Conway et al., 2015)) than smoking-related HNSCCs, and may be increasing in incidence (Chaturvedi et al., 2013; Patel et al., 2011; Koch et al., 1999; Koo et al., 2013; Katzel et al., 2015). While molecular differences between HPV positive (HPV+) and HPV− HNSCC have been described in recent years (Lleras et al., 2013; Fertig et al., 2013; Seiwert et al., 2015), molecular attributes of smoking-related, atypical, or other etiological HNSCC subgroups have not been established.