buy Sirolimus br Conclusions and future directions

Conclusions and future directions The perspective presented also suggests a number of new directions for future research that may be worth pursuing. While the notion of a unitary whole-brain adaptive response to a variety of different molecular, genetic and environmental factors discourages an overly reductionist approach to autism (see also, Johnson, 2015), it also discourages the current assumption that early infant predictive biomarkers will necessarily look like later emerging features of the diagnosis. We have previously argued that while there are clear emerging behavioral symptoms of autism evident in the second year, early predictive neurocognitive markers detectable during the first year often do not appear characteristic of these later symptoms (Johnson et al., 2015); hence, we have coined the term “antecedent” to refer to early predictors that appear unrelated in nature to the later diagnostic features. Indeed, in other cases of infant markers there may be a reversal of biomarker features between infancy and the later diagnosed condition, a hallmark of an adaptive process (Johnson et al., 2015). Turning to genetic analyses of autism and related neurodevelopmental diagnoses such as ADHD, two general features appear to characterize investigations to date (Geschwind and Flint, 2015). First, the genetic aetiology of such conditions is complex with hundreds of different genes implicated, each in a small number of cases. Second, there is substantive overlap in these implicated genes between different neurodevelopmental conditions. From the perspective of the view advanced in this paper, these general observations are unsurprising in that we should expect a variety of genes associated with synaptic plasticity (adaptation) to be common across a variety of developmental conditions in which processes of buy Sirolimus or resilience are engaged. As discussed earlier, gene expression patterns between infants at-risk for autism and infants with acquired perinatal damage could be instructive.
Acknowledgements I thank my colleagues Drs Teodora Gliga and Emily Jones for extensive discussion of these issues, and co-development of some of the ideas expressed. Financial support was provided by the UK Medical Research Council and Birkbeck College.
Introduction Substantial changes occur during puberty, including social and physical development, increases in hormones and hormonal reactivity, and related neurobiological development. These changes are widely argued to render this period of life a sensitive period in terms of risk for mental health problems (Ladouceur et al., 2012; Paus et al., 2008). However, there are two separate phases in pubertal development: adrenarche, which is triggered by the maturation of the zona reticularis of the adrenal gland, and gonadarche, associated with the maturation of the hypothalamic-pituitary-gonadal axis. A link between puberty and mental health has been mainly demonstrated with respect to the second phase of pubertal development, gonadarche, which begins with the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus at approximately 10–11 years of age, and triggers a rise in testosterone and estradiol, the maturation of primary and secondary sexual characteristics, and menarche in girls (Dorn, 2006). Individual differences in puberty can be measured in three ways. First, pubertal status, the developmental stage at which an individual is at a given point of time, can be measured by physical characteristics such as Tanner stage. Tanner stage can be assessed via self-report, parent-report, or a physical examination by a physician. Second, pubertal timing, which is pubertal status relative to same-age and −sex peers, can be measured by comparing stage/status via physical characteristics to peers, or by comparing levels of pubertal hormones to peers. Third, pubertal tempo, which is how quickly an individual passes through pubertal stages, can be measured over time (i.e., longitudinally) to examine the rate of maturation via physical characteristics or levels of hormones. We note that there is a paucity of studies that examine pubertal tempo in relation to mental health. Pubertal stage (gonadarche), on the other hand, has shown to be associated with mental health (Angold et al., 1998; Oldehinkel et al., 2011), and, in particular, it is pubertal timing that appears to be especially salient in predicting the onset of mental health problems (e.g., Angold and Costello, 2006; Kaltiala-Heino et al., 2003b; Mendle et al., 2010), and may be associated with different symptoms compared to pubertal stage alone (Oldehinkel et al., 2011). Early timing of gonadarche has been associated with depression (Copeland et al., 2010; Graber et al., 2004), anxiety (Hayward et al., 1992; Patton et al., 1996; Zehr et al., 2007), and eating (Zehr et al., 2007) and behavioral disorders (Copeland et al., 2010; Lynne et al., 2007; Stattin and Magnusson, 1990), especially for girls (Ge et al., 2001b), while the evidence for boys is more mixed (Ge et al., 2001a; Graber et al., 1997; Kaltiala-Heino et al., 2003a).