Abstract-Offspring born to mothers with hypertensive pregnancy have higher childhood blood pressure. We hypothesized this relates to prenatally programmed differences in the underlying vascular pathophysiology of the offspring and that these would be most apparent in those born preterm because of severe hypertension. We carried out a 20-year follow-up study of 71 subjects born preterm, 19 to a hypertensive pregnancy and 52 to a normotensive pregnancy. Findings were compared with 38 subjects born at term to uncomplicated pregnancies. Peripheral and central blood pressures were measured, and then central arterial stiffness was assessed by carotid-femoral pulse wave velocity using applanation tonometry. Ultrasound was used to assess flow-mediated endothelial-dependent and independent brachial artery responses and common carotid artery intima-media thickness. Key Words: blood pressure Ⅲ preeclampsia Ⅲ endothelial function Ⅲ fetal programming Ⅲ prematurity D e novo onset hypertension affects 5% to 7% of all pregnancies 1 and is manifest as a spectrum of hypertensive complications ranging from gestational hypertension to severe preeclampsia. 2 Hypertensive pregnancy has 3,4 emerged as an independent risk factor for premature maternal cardiovascular disease, 1,5,6 and recently offspring of hypertensive pregnancies have also been found to be at greater risk of higher blood pressure in childhood 7-11 and stroke in later life. 12 Furthermore, the risk to the offspring is graded and greatest in those whose mothers had more severe hypertensive signs, such as early onset hypertension or preeclampsia. 12 Severe hypertensive pregnancy is commonly associated with premature delivery and intrauterine growth restriction. 13 Prematurity and growth restriction, in turn, have been independently linked with hypertension and cardiovascular complications in the offspring, 14 -16 and it is postulated that this is mediated through intrauterine conditions adversely affecting the development of the offspring vascular system. 17 Interestingly, despite both prematurity and intrauterine growth restriction leading to the same clinical sequelae of hypertension, the persistent underlying vascular phenotype appears to vary with, for example, only the term intrauterine growthrestricted offspring exhibiting endothelial dysfunction. 15,18 -20 Better understanding of the long-term changes in vascular pathophysiology related to different pregnancy complications may allow novel primary cardiovascular prevention strategies targeted at key aspects of vascular function. 21

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Recent conceptualisations of resilience have advanced the notion that it is a dynamic and multifaceted construct. However, its adaptive components, especially those forged by adversity, have not been fully realised, and its neurobiological and psychosocial underpinnings are yet to be meaningfully integrated. In part, this is because a developmental perspective is often neglected in the formulation of resilience. In this review, we consider the findings of resilience research, with a specific emphasis on the developmental period of adolescence. To bridge the gaps in our current understanding, we propose a model of resilience that is predicated on experiencing adversity. Specifically, our model provides a sophisticated insight into the components of resilience, which, together with intrinsic features, involves facilitation of, and skill acquisition via strengthening processes we term tempering and fortification. The model also points to the potential trajectories of adversity-driven resilience and forms the basis of a framework that allows for individual variance in resilience, and the identification of both neurobiological and psychosocial targets for prevention and therapeutic interventions.

Hypersecretion of cortisol can be detected in asymptomatic individuals at genetic risk of depression and may represent an illness endophenotype. Further studies will be needed to find out if increased waking salivary cortisol levels can predict individual risk of illness and whether the increased cortisol secretion has implications for general health and cognitive function.

Suicide is complex, and it is evident that a multidimensional and integrated approach is required to reduce its prevalence. The proposed model exposes and provides access to components of the suicide process that are potentially measurable and may serve as novel and specific therapeutic targets for interventions in the context of bipolar disorder. Thus, this model is useful not only for research purposes, but also for future real-world clinical practice.

Hypersecretion of cortisol can be detected in asymptomatic individuals at genetic risk of depression and may represent an illness endophenotype. Further studies will be needed to find out if increased waking salivary cortisol levels can predict individual risk of illness and whether the increased cortisol secretion has implications for general health and cognitive function.

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