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.

We examined puberty-specific effects on affect-related behavior and on the psychophysiology of defensive and appetitive motivation while controlling for age. Adolescents (N=94, ages=12 and 13 years), viewed 75 pictures (IAPS: pleasant, neutral and aversive) while listening to auditory probes. Startle response and postauricular (PA) reflex were collected as measures of defensive and appetitive motivation respectively. Pubertal status and measures of anxiety/stress reaction and sensation/thrill seeking were obtained. Mid/late pubertal adolescents showed enhanced startle amplitude across all picture valences. A puberty by valence interaction revealed that mid/late pubertal adolescents showed appetitive potentiation of the PA, while pre/early pubertal adolescents showed no modulation of the PA reflex. Mid/late pubertal adolescents also scored significantly higher on measures of sensation/ thrill seeking than did their pre/early pubertal peers and puberty moderated the association between psychophysiology and behavioral measures, suggesting that it plays a role in reorganizing defensive and appetitive motivational systems.

This study sought to test whether the neurobiology of self-processing differentiated depressed adolescents with high suicidality from those with low suicidality and healthy controls (N=119, MAGE= 14.79, SD=1.64, Min=11.3, Max = 17.8). Participants completed a visual self-recognition task in the scanner during which they identified their own or an unfamiliar adolescent face across three emotional expressions (happy, neutral or sad). A 3 Group (HS, LS, HC) by two within subject factors [2 Self conditions (self, other) and 3 Emotions (happy, neutral, sad)] GLM yielded: 1) a main effect of Self condition with all participants showing higher activity in the right occipital, precuneus and fusiform during the self-versus other-face conditions; 2) a main effect of Group where all depressed youth showed higher dorsolateral prefrontal cortex activity than HC across all conditions, and with HS showing higher cuneus and occipital activity versus both LS and HC; and 3) a Group by Self by Emotion interaction with HS showing lower activity in both mid parietal, limbic and prefrontal areas in the Happy self versus other-face condition relative to the LS group, who in turn had less activity compared to HC youth. Covarying for depression severity replicated all results except the third finding; in this subsequent analysis, a Group by Self interaction showed that although HC had similar midline cortical structure (MCS) activity for all faces, LS showed higher MCS activity for the self vs. other faces while HS showed the opposite pattern. Results suggest that the neurophysiology of emotionally charged self-referential information can distinguish depressed, suicidal youth versus non-suicidal depressed and healthy adolescents. Neurophysiological differences and implications for the prediction of suicidality in youth are discussed. General Scientific Summary: Depressed adolescents with high suicidality show less activity in brain areas that support emotional experiences and self-awareness when identifying their own face, suggesting that abnormal self-processing may be associated with greater suicide risk.

A film paradigm was developed to examine baseline and emotion modulated startle across a broad age range from preschool to adulthood. The paradigm was tested in children (3-, 5-, 7- and 9-year-olds) and adults (total N =122). The paradigm elicited a similar startle potentiation pattern across age groups; however, baseline startle changed with age: 3- and 5-year olds showed lower response probability and magnitude of baseline startle than adults. Females exhibited larger baseline startle response probability and overall magnitude than did males; however, no sex by emotion modulated startle interaction was noted. Anxiety measures were obtained for all children. Individual differences in anxiety were associated with baseline startle magnitude among older but not younger children. No association of anxiety with startle potentiation was noted. Overall the film paradigm was applicable across a wide developmental span, revealing potential developmental and gender differences in baseline startle magnitude and response probability.