Stress and reward: A multimodal assessment of childhood sexual abuse.

Background: Childhood adversity has been found to impact stress and brain reward systems but it is unclear whether interactions between these systems might explain resilient vs. non-resilient trajectories following childhood sexual abuse (CSA). To address this gap, we adopted a multimodal approach in which cortisol reactivity to an acute stressor was assessed in conjunction with behavioral and neural measures of reward responsiveness in females with major depressive disorder (MDD) or no psychiatric disorders (i.e., resilient) who experienced CSA compared to females with and without MDD who did not experience abuse. Methods: Latent Class Mixed Modelling (LCMM) identified classes of adults (n = 62; MAge = 26.48, SD = 5.68) characterized by distinct cortisol trajectories in response to a combined social evaluative cold pressor task. Classes were examined for their history of CSA and resilience as well as behavioral and neural measures of reward responsiveness using 128-channel electroencephalography (event-related potentials and source localization analysis). Results: LCMM analysis identified two distinct classes of individuals with increased (Responders) or blunted (Non-Responders) cortisol reactivity to an acute stressor. Unlike Responders, Non-Responders did not modulate reward responses throughout the stress manipulation. No differences emerged between Responders and Non-Responders in terms of CSA or resilience. However, exploratory results showed that blunted cortisol response and non-modulation of reward responses emerged for those who experienced CSA at a younger age. Conclusions: Co-occurring blunted stress and reward reactivity emerged irrespective of adults' experience of CSA or resilience. However, preliminary findings showed that CSA ending during peripubertal development was associated with blunted cortisol and reward responsiveness. Future research needs to replicate findings in larger samples and could investigate if increasing reward responsiveness during critical times of neurodevelopment could normalize stress reactivity to future stressors and thus promote resilience.

Resting state brain dynamics: Associations with childhood sexual abuse and major depressive disorder.

Early life stress (ELS) and major depressive disorder (MDD) share neural network abnormalities. However, it is unclear how ELS and MDD may separately and/or jointly relate to brain networks, and whether neural differences exist between depressed individuals with vs without ELS. Moreover, prior work evaluated static versus dynamic network properties, a critical gap considering brain networks show changes in coordinated activity over time. Seventy-one unmedicated females with and without childhood sexual abuse (CSA) histories and/or MDD completed a resting state scan and a stress task in which cortisol and affective ratings were collected. Recurring functional network co-activation patterns (CAPs) were examined and time in CAP (number of times each CAP is expressed) and transition frequencies (transitioning between different CAPs) were computed. The effects of MDD and CSA on CAP metrics were examined and CAP metrics were correlated with depression and stress-related variables. Results showed that MDD, but not CSA, related to CAP metrics. Specifically, individuals with MDD (N = 35) relative to HCs (N = 36), spent more time in a posterior default mode (DMN)-frontoparietal network (FPN) CAP and transitioned more frequently between posterior DMN-FPN and prototypical DMN CAPs. Across groups, more time spent in a posterior DMN-FPN CAP and greater DMN-FPN and prototypical DMN CAP transition frequencies were linked to higher rumination. Imbalances between the DMN and the FPN appear central to MDD and might contribute to MDD-related cognitive dysfunction, including rumination. Unexpectedly, CSA did not modulate such dysfunctions, a finding that needs to be replicated by future studies with larger sample sizes.

Emerging ecophenotype: reward anticipation is linked to high-risk behaviours after sexual abuse.

Adolescents frequently engage in high-risk behaviours (HRB) following childhood sexual abuse (CSA). Aberrant reward processes are implicated in HRB, and their underlying fronto-striatal networks are vulnerable to neurodevelopmental changes during adversity representing a promising candidate for understanding links between CSA and HRB. We examined whether fronto-striatal responses during reward anticipation and feedback (i) are altered in depressed adolescents with CSA compared to depressed, non-abused peers and (ii) moderate the relationship between CSA and HRB irrespective of depression. Forty-eight female adolescents {14 with CSA and depression [CSA + major depressive disorder (MDD)]; 17 with MDD but no CSA (MDD); 17 healthy, non-abused controls} completed a monetary reward task during functional magnetic resonance imaging. No differences in fronto-striatal response to reward emerged between CSA + MDD and MDD. Critically, high left nucleus accumbens activation during reward anticipation was associated with greater HRB in CSA + MDD compared to MDD and controls. Low left putamen activation during reward feedback was associated with the absence of HRB in CSA + MDD compared to MDD. Striatal reward responses appear to play a key role in HRB for adolescents with CSA irrespective of depression, providing initial support for a CSA ecophenotype. Such information is pivotal to identify at-risk youth and prevent HRB in adolescents after CSA.

Exploration of baseline and early changes in neurocognitive characteristics as predictors of treatment response to bupropion, sertraline, and placebo in the EMBARC clinical trial.

BACKGROUND: Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner. METHODS: In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16. RESULTS: Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline. CONCLUSION: These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.

Frontostriatal and Dopamine Markers of Individual Differences in Reinforcement Learning: A Multi-modal Investigation.

Prior studies have shown that dopamine (DA) functioning in frontostriatal circuits supports reinforcement learning (RL), as phasic DA activity in ventral striatum signals unexpected reward and may drive coordinated activity of striatal and orbitofrontal regions that support updating of action plans. However, the nature of DA functioning in RL is complex, in particular regarding the role of DA clearance in RL behavior. Here, in a multi-modal neuroimaging study with healthy adults, we took an individual differences approach to the examination of RL behavior and DA clearance mechanisms in frontostriatal learning networks. We predicted that better RL would be associated with decreased striatal DA transporter (DAT) availability and increased intrinsic functional connectivity among DA-rich frontostriatal regions. In support of these predictions, individual differences in RL behavior were related to DAT binding potential in ventral striatum and resting-state functional connectivity between ventral striatum and orbitofrontal cortex. Critically, DAT binding potential had an indirect effect on reinforcement learning behavior through frontostriatal connectivity, suggesting potential causal relationships across levels of neurocognitive functioning. These data suggest that individual differences in DA clearance and frontostriatal coordination may serve as markers for RL, and suggest directions for research on psychopathologies characterized by altered RL.

Demonstrating test-retest reliability of electrophysiological measures for healthy adults in a multisite study of biomarkers of antidepressant treatment response.

Growing evidence suggests that loudness dependency of auditory evoked potentials (LDAEP) and resting EEG alpha and theta may be biological markers for predicting response to antidepressants. In spite of this promise, little is known about the joint reliability of these markers, and thus their clinical applicability. New standardized procedures were developed to improve the compatibility of data acquired with different EEG platforms, and used to examine test-retest reliability for the three electrophysiological measures selected for a multisite project-Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC). Thirty-nine healthy controls across four clinical research sites were tested in two sessions separated by about 1 week. Resting EEG (eyes-open and eyes-closed conditions) was recorded and LDAEP measured using binaural tones (1000 Hz, 40 ms) at five intensities (60-100 dB SPL). Principal components analysis of current source density waveforms reduced volume conduction and provided reference-free measures of resting EEG alpha and N1 dipole activity to tones from auditory cortex. Low-resolution electromagnetic tomography (LORETA) extracted resting theta current density measures corresponding to rostral anterior cingulate (rACC), which has been implicated in treatment response. There were no significant differences in posterior alpha, N1 dipole, or rACC theta across sessions. Test-retest reliability was .84 for alpha, .87 for N1 dipole, and .70 for theta rACC current density. The demonstration of good-to-excellent reliability for these measures provides a template for future EEG/ERP studies from multiple testing sites, and an important step for evaluating them as biomarkers for predicting treatment response.

Neural Correlates of Three Promising Endophenotypes of Depression: Evidence from the EMBARC Study.

Major depressive disorder (MDD) is clinically, and likely pathophysiologically, heterogeneous. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes. Guided by the NIMH Research Domain Criteria initiative, we used source localization of scalp-recorded EEG resting data to examine the neural correlates of three emerging endophenotypes of depression: neuroticism, blunted reward learning, and cognitive control deficits. Data were drawn from the ongoing multi-site EMBARC study. We estimated intracranial current density for standard EEG frequency bands in 82 unmedicated adults with MDD, using Low-Resolution Brain Electromagnetic Tomography. Region-of-interest and whole-brain analyses tested associations between resting state EEG current density and endophenotypes of interest. Neuroticism was associated with increased resting gamma (36.5-44 Hz) current density in the ventral (subgenual) anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC). In contrast, reduced cognitive control correlated with decreased gamma activity in the left dorsolateral prefrontal cortex (dlPFC), decreased theta (6.5-8 Hz) and alpha2 (10.5-12 Hz) activity in the dorsal ACC, and increased alpha2 activity in the right dlPFC. Finally, blunted reward learning correlated with lower OFC and left dlPFC gamma activity. Computational modeling of trial-by-trial reinforcement learning further indicated that lower OFC gamma activity was linked to reduced reward sensitivity. Three putative endophenotypes of depression were found to have partially dissociable resting intracranial EEG correlates, reflecting different underlying neural dysfunctions. Overall, these findings highlight the need to parse the heterogeneity of MDD by focusing on promising endophenotypes linked to specific pathophysiological abnormalities.

Reward Responsiveness Varies by Smoking Status in Women with a History of Major Depressive Disorder.

Major depressive disorder (MDD) and nicotine dependence are highly comorbid, with studies showing that ~50% of individuals with MDD smoke. The link between these disorders persists even after the clinical symptoms of depression subside, as indicated by high levels of nicotine dependence among individuals with remitted depression (rMDD). Recent evidence indicates that individuals with rMDD show blunted responses to reward as measured by a probabilistic reward task (PRT), which assesses the ability to modify behavior as a function of reward history. Given nicotine's ability to enhance reward responsiveness, individuals with rMDD might smoke to address this persistent reward deficit. However, it is unclear whether smokers with rMDD show enhanced reward responsiveness relative to rMDD individuals who do not smoke. To test this hypothesis, we evaluated reward responsiveness on the PRT in four groups (N=198): individuals with and without rMDD who were or were not nicotine dependent. As hypothesized, rMDD nonsmokers had lower reward responsiveness relative to both control nonsmokers and rMDD smokers; conversely, smokers with rMDD showed behavioral patterns comparable to those without a history of depression. Given nicotine's ability to enhance reward sensitivity, it is possible that nicotine normalizes the otherwise blunted reward responsiveness in individuals with rMDD. Therapies aimed at enhancing this reward-based deficit may be beneficial in the treatment of both nicotine dependence and MDD.

Potentiated processing of negative feedback in depression is attenuated by anhedonia.

BACKGROUND: Although cognitive theories of depression have postulated enhanced processing of negatively valenced information, previous EEG studies have shown both increased and reduced sensitivity for negative performance feedback in MDD. To reconcile these paradoxical findings, it has been speculated that sensitivity for negative feedback is potentiated in moderate MDD, but reduced in highly anhedonic subjects. The goal of this study was to test this hypothesis by analyzing the feedback-related negativity (FRN), frontomedial theta power (FMT), and source-localized anterior midcingulate cortex (aMCC) activity after negative feedback. METHODS: Fourteen unmedicated participants with Major Depressive Disorder (MDD) and 15 control participants performed a reinforcement learning task while 128-channel Electroencephalogram (EEG) was recorded. FRN, FMT, and LORETA source-localized aMCC activity after negative and positive feedback were compared between groups. RESULTS: The MDD group showed higher FRN amplitudes and aMCC activation to negative feedback than controls. Moreover, aMCC activation to negative feedback was inversely related to self-reported anhedonia. In contrast, self-reported anxiety correlated with feedback-evoked frontomedial theta (FMT) within the depression group. CONCLUSIONS: The present findings suggest that, among depressed and anxious individuals, enhanced processing of negative feedback occurs relatively early in the information processing stream. These results extend prior work and indicate that although moderate depression is associated with elevated sensitivity for negative feedback, high levels of anhedonia may attenuate this effect.

Sensitive periods of amygdala development: the role of maltreatment in preadolescence.

The amygdala is vulnerable to stress-dependent disruptions in neural development. Animal models have shown that stress increases dendritic arborization leading to larger amygdala volumes. Human studies of early stress and amygdala volume, however, remain inconclusive. This study compared amygdala volume in adults with childhood maltreatment to that in healthy controls. Eighteen participants from a longitudinal cohort and 33 cross-sectional controls (17 M/34 F, 25.5±3.1 years) completed a structural magnetic resonance imagining scan and the Maltreatment and Abuse Chronology of Exposure scale. Random forest regression with conditional trees was used to assess relative importance of exposure to adversity at each age on amygdala, thalamic or caudate volume. Severity of exposure to adversity across age accounted for 27% of the variance in right amygdala volume. Peak sensitivity occurred at 10-11 years of age, and importance of exposure at this time was highly significant based on permutation tests (p=0.003). The regression model showed that exposure during this sensitive period resulted in steep dose-response function with maximal response to even modest levels of exposure. Subjects in the highest exposure quartile (MACE-11, range=11-54) had a 9.1% greater right amygdala volume than subjects in the lowest exposure quartile (MACE-11, ≤3.5). No associations emerged between age of exposure and volume of the left amygdala or bilateral caudate or thalamus. Severity of adversity experienced at age 10-11 contributed to larger right but not left amygdala volume in adulthood. Results provide preliminary evidence that the amygdala may have a developmental sensitive period in preadolescence.

Peril and pleasure: an rdoc-inspired examination of threat responses and reward processing in anxiety and depression.

As a step toward addressing limitations in the current psychiatric diagnostic system, the National Institute of Mental Health recently developed the Research Domain Criteria (RDoC) to stimulate integrative research-spanning self-report, behavior, neural circuitry, and molecular/genetic mechanisms-on core psychological processes implicated in mental illness. Here, we use the RDoC conceptualization to review research on threat responses, reward processing, and their interaction. The first section of the manuscript highlights the pivotal role of exaggerated threat responses-mediated by circuits connecting the frontal cortex, amygdala, and midbrain-in anxiety, and reviews data indicating that genotypic variation in the serotonin system is associated with hyperactivity in this circuitry, which elevates the risk for anxiety and mood disorders. In the second section, we describe mounting evidence linking anhedonic behavior to deficits in psychological functions that rely heavily on dopamine signaling, especially cost/benefit decision making and reward learning. The third section covers recent studies that document negative effects of acute threats and chronic stress on reward responses in humans. The mechanisms underlying such effects are unclear, but the fourth section reviews new optogenetic data in rodents indicating that GABAergic inhibition of midbrain dopamine neurons, driven by activation of the habenula, may play a fundamental role in stress-induced anhedonia. In addition to its basic scientific value, a better understanding of interactions between the neural systems that mediate threat and reward responses may offer relief from the burdensome condition of anxious depression.

Co-Occurring Depressive and Substance Use Disorders in Adolescents: An Examination of Reward Responsiveness During Treatment.

The goals of the present study were to examine: (a) putative dysfunctions in reward responsiveness in a sample of adolescents (n = 40) with co-occurring depressive and substance use disorders; (b) possible links between reward responsiveness and symptoms of depression, anhedonia, anxiety, and motivation for change in relation to alcohol and drug use; and (c) potential gender differences in findings. Before and after a 2-week residential treatment, adolescents completed self-report assessments of depression, anhedonia, anxiety symptoms, and motivation for change in relation to substance use. In addition, participants completed a computer-based Probabilistic Reward Task (PRT) to examine reward responsiveness (i.e., participants' ability to modulate behavior as a function of reinforcement history). Results indicated that depression and anhedonia symptoms decreased, and motivation for change in relation to drug use increased. Improved reward responsiveness over the course of residential treatment emerged in female, but not male, participants.

Blunted reward responsiveness in remitted depression.

Major depressive disorder has been associated with blunted responsiveness to rewards, but inconsistencies exist whether such abnormalities persist after complete remission. To address this issue, across two independent studies, 47 adults with remitted major depressive disorder (rMDD) and 37 healthy controls completed a Probabilistic Reward Task, which used a differential reinforcement schedule of social or monetary feedback to examine reward responsiveness (i.e., ability to modulate behavior as a function of reinforcement history). Relative to controls, adults with rMDD showed blunted reward responsiveness. Importantly, a history of depression predicted reduced reward learning above and beyond residual depressive (including anhedonic) symptoms and perceived stress. Findings indicate that blunted reward responsiveness endures even when adults are in remission and might be a trait-related abnormality in MDD. More research is warranted to investigate if blunted reward responsiveness may predict future depressive episodes and whether targeting reward-related deficits may prevent the re-occurrence of the disorder.

Disrupted reinforcement learning and maladaptive behavior in women with a history of childhood sexual abuse: a high-density event-related potential study.

IMPORTANCE: Childhood sexual abuse (CSA) has been associated with psychopathology, particularly major depressive disorder (MDD), and high-risk behaviors. Despite the epidemiological data available, the mechanisms underlying these maladaptive outcomes remain poorly understood. OBJECTIVE: We examined whether a history of CSA, particularly in conjunction with a past episode of MDD, is associated with behavioral and neural dysfunction in reinforcement learning, and whether such dysfunction is linked to maladaptive behavior. DESIGN: Participants completed a clinical evaluation and a probabilistic reinforcement task while 128-channel event-related potentials were recorded. SETTING: Academic setting; participants recruited from the community. PARTICIPANTS: Fifteen women with a history of CSA and remitted MDD (CSA + rMDD), 16 women with remitted MDD with no history of CSA (rMDD), and 18 healthy women (controls). EXPOSURE: Three or more episodes of coerced sexual contact (mean [SD] duration, 3.00 [2.20] years) between the ages of 7 and 12 years by at least 1 male perpetrator. MAIN OUTCOMES AND MEASURES: Participants' preference for choosing the most rewarded stimulus and avoiding the most punished stimulus was evaluated. The feedback-related negativity and error-related negativity-hypothesized to reflect activation in the anterior cingulate cortex-were used as electrophysiological indices of reinforcement learning. RESULTS: No group differences emerged in the acquisition of reinforcement contingencies. In trials requiring participants to rely partially or exclusively on previously rewarded information, the CSA + rMDD group showed (1) lower accuracy (relative to both controls and the rMDD group), (2) blunted electrophysiological differentiation between correct and incorrect responses (relative to controls), and (3) increased activation in the subgenual anterior cingulate cortex (relative to the rMDD group). A history of CSA was not associated with impairments in avoiding the most punished stimulus. Self-harm and suicidal behaviors correlated with poorer performance of previously rewarded, but not previously punished, trials. CONCLUSIONS AND RELEVANCE: Irrespective of past MDD episodes, women with a history of CSA showed neural and behavioral deficits in utilizing previous reinforcement to optimize decision making in the absence of feedback (blunted "Go learning"). Although our study provides initial evidence for reward-specific deficits associated with CSA, future research is warranted to determine if disrupted positive reinforcement learning predicts high-risk behavior following CSA.

Reactivity, regulation, and reward responses to infant cues among mothers with and without psychopathology: an fMRI review.

Despite important progress in understanding the complex caregiving system, developmental research has only recently begun to focus on the mother's internal affective state and its role in sensitive caregiving behavior. This review will summarize recent findings of functional neuroimaging research to elaborate on the neural components associated with maternal sensitive care or disrupted responsiveness to infant communications. First, maternal emotion reactivity and regulation, as well as maternal reward responsiveness to infant cues, will be reviewed among healthy mothers. Then, emotion and reward-related processes among mothers who display sensitive versus disrupted caregiving will be explored. Finally, these patterns of response will be compared to patterns of response among mothers with psychiatric disorders, including depression, posttraumatic stress disorder, and substance abuse. The aim of this review is to examine whether differences in emotion reactivity and regulation, as well as in the encoding of infant stimuli as rewarding, are related either to maternal psychopathology or to maternal difficulties in responding promptly and appropriately to their infants. A summary of the challenges facing developmental neuroscience research in furthering our understanding of maternal responses to infants will close this review.

Early Maternal Withdrawal and Nonverbal Childhood IQ as Precursors for Substance Use Disorder in Young Adulthood: Results of a 20-Year Prospective Study.

The relation between early mother-infant interaction and later socio-emotional development has been well established. The present study addresses the more recent interest in the impact of maternal caregiving on cognitive development and their role in decision-making in young adulthood. Using data from a prospective longitudinal study on attachment, prediction from early mother-infant interactions at age 18 months and from verbal and nonverbal cognitive skill at age 5 were examined as predictors of a substance use disorder (abuse/dependence) in young adulthood (age 20) on the Structured Clinical Interview for DSM-IV (SCID). Results reveal that the mother's withdrawal from interaction with the infant at age 18 months, coded using the AMBIANCE coding system (Atypical Maternal Behavior Instrument for Assessment and Classification), was associated with the child's lower nonverbal cognitive scores but not verbal cognitive scores at age 5. In addition, maternal withdrawal at 18 months predicted a clinical diagnosis of substance use disorder (alcohol/cannabis) at age 20. Finally, nonverbal reasoning at age 5 mediated the relationship between early maternal withdrawal and substance use disorder (alcohol/cannabis) in young adulthood. Findings indicate the need for further work examining how early maternal withdrawal affects nonverbal cognitive development by school entry, and how these nonverbal deficits further contribute to maladaptive coping strategies such as substance use by young adulthood.

Conceptualization of the complex outcomes of sexual abuse: a signal detection analysis.

Eighty-five New Zealand based practitioners experienced in treating adults with a history of child sexual abuse participated in an online judgment study of child sexual abuse outcomes using signal detection theory methodology. Participants' level of sensitivity was assessed independent of their degree of response bias when discriminating (a) known child sexual abuse outcomes from behaviors thought to be unrelated to child sexual abuse and (b) direct child sexual abuse effects from subsequent coping strategies. Results demonstrated good sensitivity (accuracy) when identifying child sexual abuse effects from noneffects. When asked to discriminate direct child sexual abuse effects from ways of coping with distress, practitioners' accuracy was reduced, revealing a tendency to identify all effects as coping. Although treatment approaches highlight the pivotal role of identifying coping strategies, practitioners did not perceive maladaptive coping as a distinct clinical feature. Complex abuse cases may benefit from replacing maladaptive coping strategies (e.g., self-harm) with constructive coping (e.g., social support) in order to deliver efficacious practice.

Perceived parental protection and cortisol responses among young females with borderline personality disorder and controls.

Borderline personality disorder (BPD) has been associated with deviations in cortisol in response to interpersonal stressors. Identifying mechanisms contributing to such deviations may help to address emotional dysregulation and the increased risk of self-destructive behavior. While dysfunctional relationships to caregivers have been widely reported among individuals with BPD, their contribution to cortisol hyperresponsiveness has yet to be investigated. Fifty-one females (aged 18-24years) participated to assess the impact of BPD and the quality of protective care in mother-daughter relationships on stress responsiveness. Seventeen females with BPD and twenty females without BPD participated with their mothers in a videotaped parent-young adult conflict discussion. Fourteen non-BPD females without their mothers were assessed for cortisol levels without stress exposure. Salivary cortisol samples were collected at lab entry and 20 and 40min after the onset of the discussion. Results revealed a higher overall cortisol response in the BPD group upon lab entry. BPD participants reported less experienced protection in the mother-daughter relationship which was associated with higher cortisol levels on lab entry and higher distress at study end. Results point to the perceived quality of parental protection as likely to modulate the activity of the stress response system among BPD patients.

Effects of early life stress on cognitive and affective function: an integrated review of human literature.

RATIONALE: The investigation of putative effects of early life stress (ELS) in humans on later behavior and neurobiology is a fast developing field. While epidemiological and neurobiological studies paint a somber picture of negative outcomes, relatively little attention has been devoted to integrating the breadth of findings concerning possible cognitive and emotional deficits associated with ELS. Emerging findings from longitudinal studies examining developmental trajectories of the brain in healthy samples may provide a new framework to understand mechanisms underlying ELS sequelae. OBJECTIVE: The goal of this review was twofold. The first was to summarize findings from longitudinal data on normative brain development. The second was to utilize this framework of normative brain development to interpret changes in developmental trajectories associated with deficits in cognitive and affective function following ELS. RESULTS: Five principles of normative brain development were identified and used to discuss behavioral and neural sequelae of ELS. Early adversity was found to be associated with deficits in a range of cognitive (cognitive performance, memory, and executive functioning) and affective (reward processing, processing of social and affective stimuli, and emotion regulation) functions. CONCLUSION: Three general conclusions emerge: (1) higher-order, complex cognitive and affective functions associated with brain regions undergoing protracted postnatal development are particularly vulnerable to the deleterious effects of ELS; (2) the amygdala is particularly sensitive to early ELS; and (3) several deficits, particularly those in the affective domain, appear to persist years after ELS has ceased and may increase risk for later psychopathology.

An empirical taxonomy of social-psychological risk indicators in youth suicide .

The current study integrates descriptive (though primarily social-psychological) statements about youth suicide into a coherent, empirically supported taxonomy. Drawing from relevant literature, a set of 107 items characterizing these contributions about youth suicide was created. Seventy-two participants sorted these statements according to their "face-value" by following two separate procedures. Analyses of these two data sets using multi-dimensional scaling resulted in a common "map" depicting inter-item (dis)similarities. Non-arbitrary rotation of this map revealed three bipolar and orthogonal dimensions labelled as under- and overengagement, rejection-turmoil, and self- to death-identification. It is suggested this dimensional analysis could provide a viable frame for examining and interpreting descriptions about suicide risk and may serve to extend theoretical accounts.