Stress is a part of every life to varying degrees, but individuals differ in their stress vulnerability. Stress is usefully viewed from a biological perspective; accordingly, it involves activation of neurobiological systems that preserve viability through change or allostasis. Although they are necessary for survival, frequent neurobiological stress responses increase the risk of physical and mental health problems, perhaps particularly when experienced during periods of rapid brain development. Recently, advances in noninvasive measurement techniques have resulted in a burgeoning of human developmental stress research. Here we review the anatomy and physiology of stress responding, discuss the relevant animal literature, and briefly outline what is currently known about the psychobiology of stress in human development, the critical role of social regulation of stress neurobiology, and the importance of individual differences as a lens through which to approach questions about stress experiences during development and child outcomes.

Background-Bipolar disorder is frequently misdiagnosed as major depressive disorder delaying appropriate treatment and worsening outcome for many bipolar individuals. Emotion dysregulation is a core feature of bipolar disorder. Measures of dysfunction in neural systems supporting emotion regulation may therefore help discriminate bipolar from major depressive disorder.

Post-traumatic stress disorder (PTSD) is associated with functional abnormalities of the hypothalamic-pituitary-adrenocortical (HPA) axis. Emerging evidence suggests that failures in social regulation of the HPA axis in young children manifested as neglectful or abusive care may play a role in shaping cortico-limbic circuits involved in processing experiences threatening experiences encountered later in life. Low cortisol levels, particularly near the peak of the diurnal rhythm, have been reported in abused, neglected and deprived children. Thus early imprinting effects of parenting quality on the HPA system regulation may be one of the mechanisms causing heightened risk of PTSD in responses to later trauma. However there is also evidence that the altered patterns of cortisol production seen in the context of early adverse care are not permanent, and remit once the care children receive improves. What awaits study is whether periods of atypical cortisol levels and altered HPA function early in life, even if transient, impact brain development in ways that heighten vulnerability to PTSD in response to traumas experienced later.

Objectives The absence of pathophysiologically relevant diagnostic markers of bipolar disorder (BD) leads to its frequent misdiagnosis as unipolar depression (UD). We aimed to determine whether whole brain white matter connectivity differentiated BD from UD depression. Methods We employed a three-way analysis of covariance, covarying for age, to examine whole brain fractional anisotropy (FA), and corresponding longitudinal and radial diffusivity, in currently depressed adults: 15 with BD-type I (mean age 36.3 years, SD 12.0 years), 16 with recurrent UD (mean age 32.3 years, SD 10.0 years), and 24 healthy control adults (HC) (mean age 29.5 years, SD 9.43 years). Depressed groups did not differ in depression severity, age of illness onset, and illness duration. Results There was a main effect of group in left superior and inferior longitudinal fasciculi (SLF and ILF) (all F ≥ 9.8; p ≤ .05, corrected). Whole brain post hoc analyses (all t ≥ 4.2; p ≤ .05, corrected) revealed decreased FA in left SLF in BD, versus UD adults in inferior temporal cortex and, versus HC, in primary sensory cortex (associated with increased radial and decreased longitudinal diffusivity, respectively); and decreased FA in left ILF in UD adults versus HC. A main effect of group in right uncinate fasciculus (in orbitofrontal cortex) just failed to meet significance in all participants but was present in women. Post hoc analyses revealed decreased right uncinate fasciculus FA in all and in women, BD versus HC. Conclusions White matter FA in left occipitotemporal and primary sensory regions supporting visuospatial and sensory processing differentiates BD from UD depression. Abnormally reduced FA in right fronto-temporal regions supporting mood regulation, might underlie predisposition to depression in BD. These measures might help differentiate pathophysiologic processes of BD versus UD depression.

Associations between early deprivation/neglect in the form of institutional care with the cortisol awakening response (CAR) were examined as a function of pubertal status among 12- and 13-year-old post-institutionalized youth. CARs indexed hypothalamic-pituitary-adrenocortical reactivity. Post-institutionalized youth were compared to youth adopted internationally from foster care (adoption control) and to nonadopted youth reared in families comparable in parental education and income to the adoptive families. Post-institutionalized youth exhibited a blunted CAR if they were at earlier but not if they were at later stages of puberty. Similarly, for both groups of internationally adopted youth combined, earlier but not later stages of puberty were associated with more blunted CARs at higher but not lower levels of parent-reported pre-adoption physical and social neglect.