A review of childhood maltreatment,latent vulnerability and the brain: implications for clinical practice and prevention

Abstract

There is a well-established association between childhood maltreatment and later poor mental health and increasing recognition that we need to find ways to support children following such experiences to improve long-term outcomes. We suggest that the rationale for such a preventive approach is directly informed by the emerging findings from the field of functional neuroimaging. Here, we review the evidence from four neurocognitive systems: threat processing, reward processing, emotion regulation and executive control. We briefly summarise what is known about each system, review the evidence that altered functioning is implicated in common mental health problems and describe how the functioning of each system is altered following maltreatment. Across domains, these neurocognitive alterations following child maltreatment are in line with those seen in adults presenting with mental health problems yet most maltreated children studied do not have a presenting ‘disorder’. This suggests that these neurocognitive alterations may potentiate the risk of future psychopathology. We discuss this possibility in the context of the theory of latent vulnerability (McCrory and Viding, 2015). According to this model, children may respond to early adverse environments in ways that are potentially adaptive in the short term but which create vulnerability to future mental health problems in the long term. We also consider the clinical implications of the neuroimaging evidence ‒ in particular, the growing need for a more preventive clinical approach.

Keywords

Child abuse maltreatment mental health functional magnetic resonance imaging resilience

Introduction

Childhood maltreatment, including physical, emotional, sexual abuse and neglect, are relatively common forms of adversity. Each year, in high-income countries about one percent of children are referred to child protection services (Radford, et al., 2011). However, the official rates of substantiated maltreatment seem to be just the tip of the iceberg. Self-reported measures suggest a much larger proportion of individuals experience abuse, neglect or are exposed to domestic violence during childhood (Gilbert, et al., 2009; Radford, et al., 2011). These negative early life experiences are associated with a wide range of negative outcomes, including reduced economical productivity, educational attainment and physical health (Gilbert, et al., 2009). Moreover, recent longitudinal work suggests that childhood maltreatment is one of the most potent predictors of poor mental health across the lifespan (Vachon, et al., 2015; Widom, et al., 2007). Population-attributable risk assessments from large cross-cultural studies, which assume the existence of a direct causal link between childhood maltreatment and future psychopathology, estimate that abuse and neglect account for a large proportion of psychological disorders onset during childhood and also adulthood (Green, et al., 2010).

Despite the well-established association between childhood maltreatment and increased risk for psychopathology (Gilbert, et al., 2009; Vachon, et al., 2015), we do not know enough about the neurocognitive mechanisms by which increased vulnerability becomes embedded. Nor do we have a detailed understanding about what factors may promote resilience (Rutter, 2012). We need to better comprehend how maltreatment alters psychological and neurobiological functioning in ways that increase risk of mental health problems. Equally, we need to understand the intrinsic and extrinsic individual characteristics that can promote a positive outcome despite early adversity. These gaps in our understanding leave clinicians and professionals who work within child protection services without adequate resources and knowledge that would allow them to identify and provide support for those individuals most likely to develop mental health difficulties in the future (McCrory, et al., 2017).

Service provision in the UK has been primarily organised around a medical diagnostic model which assumes that individuals with similar clinical presentation are comparable. The evidence suggests that this is not the case (Nanni, et al., 2012). Moreover, the systemic, attachment, social and educational needs of children are often not dealt with holistically alongside symptom presentation. Such an approach has limited the scope for clinicians to develop an understanding of how disorders emerge and unfold across development within complex systems. Although we know a lot about the risk and resilience factors associated with mental health problems, we still have a limited understanding of the mechanisms that shape how they develop following childhood maltreatment. In addition, the differences across disciplines have led to the compartmentalisation of knowledge. We argue that there is a growing need for researchers, clinicians, parents, foster carers, children and social workers to work more collaboratively if progress is to be made.

The theory of latent vulnerability

In an effort to shift the focus on prevention and the developmental mechanisms associated with the emergence of mental health problems following childhood maltreatment, McCrory and Viding have proposed the theory of latent vulnerability (McCrory and Viding, 2015; McCrory, et al., 2017). This theory offers a system-level approach that places emphasis on the neurocognitive mechanisms that link childhood maltreatment to subsequent mental health problems (see Figure 1).

Figure 1.

A schematic illustration (taken from McCrory, Gerin and Viding, 2017) depicting how latent vulnerability can become instantiated at the neurocognitive level with both direct and indirect effects on socio-emotional functioning. Differential outcomes are shown in relation to mental health risk and resilience depending on protective factors, stressor exposure and genotype.

According to this account, childhood maltreatment leads to measurable alterations that can be characterised at neurobiological and cognitive levels. These changes can be understood as developmental recalibrations to negative early experiences; in other words, they are not necessarily seen as signs of ‘damage’. Rather, such changes may, in many instances, be adaptive within the context of maltreatment and confer short-term functional advantages (for example, faster detection of threat or reduced expectation of reward). However, such alterations are also thought to incur long-term costs (e.g. increased risk of psychological problem or revictimisation) as an individual may not be optimised to cope with the demands of more normative environments, such as school or a stable foster placement. Importantly, maltreatment-related patterns of adaptation are understood to be ‘latent’ as they may appear before the emergence of a mental health problem and are not necessarily manifest symptoms or precursors of any future condition.

The theory of latent vulnerability focuses on maltreatment-related neurocognitive processes that increase, non-deterministically, the risk of future difficulties. In doing so, it complements a wider research literature demonstrating that a variety of maltreatment-related emotional states (such as shame), self and other representations (such as abuse-related self-blame), and psychological states (such as dissociation) also confer risk for future difficulties (e.g. Feiring and Cleland, 2007; Hanson, 2016; Yates, et al., 2008). By focusing attention on the maltreatment-related processes and alterations that precede the emergence of more overt difficulties, this framework has the potential to increase the application of research to practice. First, a systematic investigation of the neurocognitive processes associated with increased vulnerability may help inform the development of a screening tool that could be used by frontline practitioners to identify those individuals at most risk of developing later mental health problems. Second, understanding the processes that instantiate increased vulnerability may inform the development of interventions that most effectively help to prevent maltreated children from developing subsequent mental health difficulties. Third, this understanding provides a clear rationale for rethinking service design and delivery, with a much greater focus on the prevention of mental health problems.

Functional magnetic resonance imaging studies of childhood maltreatment

This review explores changes to neurocognitive processes that may increase risk of mental health problems following maltreatment experience. A wide range of methods and paradigms has been used to investigate the neurobiological impact of childhood maltreatment. These include the measurement of neuroendocrine stress and inflammatory responses (Coelho, et al., 2014), the detection of neuroanatomical changes via Structural Magnetic Resonance Imaging (sMRI) and Diffusion Tensor Imaging (DTI) (Kelly, et al., 2015; Puetz, et al., 2017) as well as functional brain alterations using electroencephalography (EEG) (Curtis and Cicchetti, 2013) and Functional Magnetic Resonance Imaging (fMRI). In our view, task-based fMRI has the greatest potential to help refine our understanding of the underlying neurocognitive differences in processing that may not be otherwise detectable, with more direct implications for practice (e.g. Gerin, et al., 2017; McCrory, et al., 2013). Therefore, in order to focus this article, we will confine our consideration to fMRI findings, reviewing all extant fMRI studies of children and adolescents with histories of maltreatment relating to four key areas: threat processing, reward processing, emotion regulation and executive control. (We refer readers to McCrory and colleagues [2017] for a more comprehensive review and methodological critique of the literature.) To help put these findings into context, we first provide a brief description of each system and then summarise how each has been implicated in common mental health difficulties before considering the evidence from studies of maltreatment or adverse early life experience.

In brief, the studies discussed here support the notion that some individuals with histories of childhood maltreatment, even in the absence of manifest clinical symptoms, may present with changes in brain function across several cognitive, social and emotional domains. These changes are often consistent with neural signature observed in individuals with anxiety, depression and conduct problems (McCrory, et al., 2017).

1. Threat processing

What is threat processing? Survival is dependent on the ability to detect and respond to dangerous and aversive stimuli in the environment. For this reason, it is not surprising that both animal and human studies have revealed that a large amount of cognitive resources and neurobiological systems are dedicated to threat detection (LeDoux, 2000). Within the central nervous system the amygdala is one of the core structures dedicated to the processing of danger and to the detection of salient information more broadly (LeDoux, 2000). The amygdala is part of an integrated network comprising several cortical and subcortical brain regions involved in fear conditioning, stress responses and salience detention, such as the hippocampus, the striatum, the anterior insula and the dorsal anterior cingulate cortex (ACC) (Shin and Liberzon, 2010).

How is altered threat processing implicated in mental health difficulties? In recent years, neuroimaging findings have shown that alterations in amygdala and anterior insula activation are implicated in several disorders, including post-traumatic stress disorder (PTSD), mood and anxiety disorders (Etkin and Wager, 2007; Kerestes, et al., 2014; Patel, et al., 2012), drug addiction (Sripada, et al., 2011) and conduct problems (Viding, et al., 2012). Crucially, recent longitudinal studies of healthy individuals exposed to different kinds of environmental stressors have shown that baseline hyper-responsiveness (i.e. increased responsiveness) to threat in the brain is associated not just with current, but also with future symptoms (Admon, et al., 2009; Admon, Milad and Hendler, 2013; Swartz, et al., 2015).

Functional neuroimaging studies of threat processing in maltreated children and adolescents. Animal studies have established a strong link between early adverse experiences (such as early separation from a caregiver, social isolation or reduced maternal care and sensitivity) and neurophysiological long-lasting alterations in the central and peripheral nervous systems involved in threat processing and stress responses (Caldji, Diorio and Meaney, 2003; Meaney, 2001; Rosenblum, et al., 1994). Behavioural and electrophysiological studies with humans also suggest that abuse and neglect are associated with long-lasting alterations in threat processing that can be detected as early as infancy. These changes include heightened electrophysiological responses to negative stimuli and preferential attention and enhanced perceptual ability for threat cues, such as angry or fearful faces (Curtis and Cicchetti, 2013; Pollak and Sinha, 2002; Pollak, et al., 2005).

These behavioural and neurophysiological findings have been extended by a series of recent functional magnetic resonance imaging (fMRI) studies with children and adolescents. These have found a pattern of increased neural response during the processing of threat cues (e.g. angry faces) in the amygdala and other subcortical neighbouring regions, such as the anterior insula and hippocampus (Maheu, et al., 2010; McRory, et al. 2011; 2013; Tottenham, et al., 2011). Such neural alterations seem to be shared across individuals with different experiences of early adversity, ranging from severe institutional neglect (Maheu, et al., 2010; Tottenham, et al., 2011), substantiated maltreatment in community settings (McCrory, et al., 2011; 2013) and also less severe experiences of neglect (White, et al., 2012). Importantly, by using well-matched control groups, these studies suggest that increased threat-related neural responses among maltreated children and adolescents is independent from potentially confounding factors, such as IQ, socio-economic status, pubertal status and concurrent psychopathology (e.g. McCrory, et al., 2013; Maheu, et al., 2010). Moreover, by showing that both amygdala and insula hyperactivity have a dose-dependent relationship with the severity/duration of maltreatment (McCrory, et al., 2013; Maheu, et al., 2010), these findings point to a pattern of neural calibration directly related to the degree of early adversity. Finally, it is worth noting that a similar pattern of findings comes from studies with adults with a history of childhood maltreatment, suggesting that abuse and neglect can have a long-lasting impact on the threat-processing system (e.g. Dannlowski, et al., 2012).

Summary. It has been shown that different forms of early adversity alter the neural reactivity of the threat system, especially amygdala activation, even in children and adolescents who are not presenting with overt psychiatric symptomatology. Crucially, this association seems to be directly related to the severity of maltreatment (McCrory, et al., 2011; Maheu, et al., 2010; White, et al., 2012). Interestingly, similar findings have been reported in adults who experienced maltreatment during childhood (see Hein and Monk, 2016), suggesting that such alterations can be long lasting. Given that hyper-responsiveness of the amygdala and anterior insula have been associated with several psychiatric conditions, including depression, anxiety and PTSD, it is possible that altered threat processing may increase the risk of future mental health problems. However, longitudinal studies are required to confirm this hypothesis. Ways in which this risk might become instantiated are discussed in the clinical implications section below.

2. Reward processing

What is reward processing? Learning which stimuli and actions are associated with attaining rewarding objects, experiences or events is essential to motivate and guide adaptive decision-making and behaviour. The main network underpinning the processing of reward is the mesocorticolimbic dopaminergic neural pathway. This includes brain-stem regions, such as the ventral tegmental area, which project to basal ganglia nuclei, especially the striatum, and terminate in prefrontal regions, including the orbitofrontal cortex (Clithero and Rangel, 2013; O’Doherty, 2011).

How is altered reward processing implicated in mental health difficulties? Neural alterations in the reward system have been associated with suboptimal decision-making and psychological distress, such as the emergence and maintenance of anxiety, mood, conduct and substance abuse disorders (Balodis and Potenza, 2015; Stringaris, et al., 2015; White, et al., 2013; Zhang, et al., 2013). For example, neuroimaging findings show a consistent pattern of reduced activation in the striatum during reward processing among depressed individuals (Forbes and Dahl, 2012; Pizzagalli, et al., 2009; Ubl, et al., 2015). Interestingly, this predicts not only current but also future clinical status and symptoms level (Morgan, et al., 2013; Telzer, et al., 2014), even in those who were previously ‘healthy’ (Stringaris, et al., 2015). Neuroimaging studies suggest that this pattern of blunted neural activation may be associated with difficulties in computing reward anticipation and detecting differences between expected and actual rewards (prediction-error signalling). In the context of depression, this might entail reduced sensitivity to rewards and limited motivational response (i.e. anhedonia) (Gotlib, et al., 2010; Stringaris, et al., 2015; Ubl, et al., 2015); in the context of conduct disorder, this may suggest difficulties in integrating and updating reward (and punishment) information (White, et al., 2013; 2016).

Functional neuroimaging studies of reward processing in maltreated children and adolescents. Researchers have been motivated to investigate reward processing in maltreated individuals for two reasons. First, the clinical literature described above suggests that altered reward processing may be associated not just with current symptoms, but also with the development of mental health problems. Secondly, we know that the familial environment experienced by maltreated children is often characterised by the erratic and infrequent availability of rewards. To date, most neuroimaging studies of maltreatment have found reduced activation during reward processing, especially in the striatum and the orbitofrontal cortex (McCrory, et al., 2017). This pattern of findings has been found both in individuals who have experienced extreme forms of institutional deprivation (Goff, et al., 2013; Mehta, et al., 2010) or maltreatment in community settings, especially neglect (Gerin, et al., 2017; Hanson, Hariri and Williamson, 2015). Notably, this pattern of findings remains even after controlling for the presence of overt psychological disorders or symptoms severity for conditions commonly associated with blunted reward-related neural response, such as depression (e.g. Gerin, et al., 2017). Dennison and colleagues (2016) did not identify this effect but nevertheless found that higher neural response to reward was linked to better future mental health outcomes. Overall, these findings suggest that increased/decreased activation in the striatum may represent a marker of resilience/risk to psychopathology. In particular, the pattern of lower neural response in maltreated individuals may reflect neural calibration to reduced opportunities for reward-based learning. Such alterations may represent an adaptive regulatory mechanism which reduces disappointment in the context of inconsistent and insensitive parenting (McCrory, et al., 2017). However, these neurocognitive alterations may also hamper functioning in more normative situations. For example, they may hinder exploratory behaviour, thus decreasing the opportunities for learning and for motivating the search of alternative sources of reward outside the home environment.

Summary. Overall, these findings suggest that maltreatment, especially neglect and institutional deprivation, is associated with a blunted neural response to reward cues in the orbito-striatal network. This neural profile, which may be shaped by familial environments characterised by erratic and infrequent availability of rewards, is also known to be associated with common mental health problems, particularly depression and conduct disorder. Therefore, alterations in reward processing following maltreatment may represent a potential neurocognitive vulnerability to mental health difficulties. Initial longitudinal evidence also suggests that higher levels of neural response in this network may be a marker of resilience to future psychopathology.

3. Emotion regulation

What is emotion regulation? The ability to regulate affect entails the modification of an emotion by producing changes to its intensity, duration or valence (Eisenberg and Spinrad, 2004; Ochsner, Silvers and Buhle, 2012). Various strategies can be used for emotion regulation, such as emotional distancing, suppression, social support, reappraisal and attention modulation, just to mention a few (Koenigsberg, et al., 2010; Ochsner, Silvers and Buhle, 2012). Crucially, such processes may involve explicit effort or occur implicitly and outside conscious awareness (Gyurak, Gross and Etkin, 2011). A large neural network is linked to affect regulation. Broadly speaking, prefrontal regions are understood to have top-down regulatory control over regions implicated in emotional reactivity, impulsivity and negative affect, such as the amygdala, insula, striatum and the dorsal anterior cingulate cortex (dACC) (Etkin, et al., 2015; Ochsner, Silvers and Buhle, 2012). In particular, the ventral anterior cingulate cortex (vACC) and medial prefrontal cortex (mPFC) seem to be more involved in the implicit and automatic regulation of affect, while latero-prefrontal (lPFC) and also latero-parietal (lPC) cortices appear to be necessary for more explicit and volitional forms of emotion regulation (Etkin, Büchel and Gross, 2015).

How is altered emotion regulation implicated in mental health disorders? Many psychological difficulties involve altered affect regulation (e.g. anxiety, conduct disorder and depression) (Aldao, Nolen-Hoeksema and Schweizer, 2010; Mennin, et al., 2007). Moreover, difficulties in emotion regulation have been shown to represent a risk factor for developing mental health problems in the future among those individuals who have suffered early adversity (Kim-Spoon, Cichetti and Rogoscherin, 2013) and/or who do not present with current clinical symptoms (Folk, et al., 2014; Michl, et al., 2013; Wirtz, et al., 2014).

Functional neuroimaging studies of emotion regulation in children and adolescents exposed to maltreatment. Three studies of functional connectivity have reported that maltreated children and adolescents present with atypical connectivity between regulatory frontal regions (such as vACC and mPFC) and subcortical brain areas, such as the amygdala (Gee, et al., 2013; Lee, et al., 2015; Marusak, et al., 2015). In addition, five studies that investigated focal brain activity have also reported alterations in the same frontal regulatory network, including the mPFC, vACC, dACC and also the lPFC (Elsey, et al., 2015; McLaughlin, et al., 2015; Marusak, et al., 2015; Puetz, et al., 2014; 2016). However, despite the fact that these studies have reported altered functioning in a consistent set of brain regions during emotion regulation, the direction of these alterations has been inconsistent (i.e. increased vs decreased activity and stronger vs weaker connectivity). These discrepancies are not entirely unexpected given the spectrum of participants recruited in these studies. Participants varied in terms of developmental stage and type of early adversity (e.g. physical abuse, verbal abuse, institutionalisation, neglect in community settings, etc.). Moreover, different emotion regulation paradigms were implemented, with some requiring simple or automatic emotional processing and others requiring more explicit and higher order regulatory demands. It has been suggested that these different task demands may be helpful in understanding the differences across studies (McCrory, Gerin and Viding, 2017). When a task explicitly requires participants to attend to aversive stimuli or to consciously modulate affective responses (Elsey, et al., 2015; McLaughlin, et al., 2015) one tends to see a pattern of increased activation in regulatory frontal regions in maltreated individuals that may reflect increased effort. On the other hand, on those tasks where it is possible to shift attention away from the processing of aversive stimuli, maltreated individuals show a pattern of reduced activation and connectivity (Gee, et al., 2013; Lee, et al., 2015; Puetz, et al., 2014; 2016). This pattern of hypo-activation is consistent with the use of avoidant and dissociative regulatory strategies (McCrory, Gerin and Viding, 2017) that can often be unhelpful in the longer term and are associated with increased risk of anxiety, depression, self-harm and PTSD (Kaplow, et al., 2005; Karstoft, et al., 2015; Wirtz, et al., 2014; Yates, et al., 2008).

Summary. Overall, the neuroimaging studies of emotion regulation in maltreated children and adolescents suggest that the network traditionally involved in self-regulatory processes shows a pattern of atypical focal activation and connectivity. Medial frontal regions (e.g. vACC and mPFC) and the lPFC seem to be particularly implicated, as well as the frontolimbic neural network (e.g. amygdala-vACC connectivity). Taken together with the neuroimaging studies of mental health disorders, these findings suggest that emotion regulation processing changes may confer risk. However, longitudinal studies are still required to test this hypothesis directly. The heterogeneity in the neurocognitive findings to date probably reflects differences in the type and timing of early adversity and the specific computations (simply put, explicit vs implicit) engaged during different emotion regulation tasks.

4. Executive control

What is executive control? Executive control broadly refers to three interrelated cognitive functions: inhibiting (the ability to constrain automatic and dominant responses irrelevant to a given goal), updating (the ability to maintain, monitor and quickly add/delete information) and shifting (the ability to flexibly switch between different tasks) (Miyake, et al., 2000). These functions are important for adaptive behaviour and effective decision-making. Neuroimaging studies have found that these functions are underpinned by a central executive network whose central nodes include the dorsolateral prefrontal cortex (dlPFC) and posterior parietal cortex. Brain areas engaged during error monitoring, such as the dACC and mid cingulate cortex (MCC), are also involved in executive control functions.

How is altered executive control implicated in mental health difficulties? Cross-sectional and longitudinal evidence suggests that alterations in executive control may be involved in the development of depression, anxiety, conduct problems, ADHD and PTSD (Cortese, et al., 2012; Evans, et al., 2015; Parslow and Jorm, 2007; Snyder, Kaiser, et al., 2015). The association between atypical executive control and mental health problems may (for example) be mediated by alterations in several cognitive, emotional and social processes which rely upon executive functions, such as suppression of ruminative thinking, problem-solving and regulation of affect (Snyder, Miyake, et al., 2015).

Functional neuroimaging studies of executive control in maltreated children and adolescents. Two studies have found that exposure to early adversity is associated with increased activation during tasks requiring executive functions (such as error processing, cognitive shifting and inhibition) in brain areas linked with executive control, including the dACC/MCC and lateral frontal regions (Lim, et al., 2015; Mueller, et al., 2010). This increased activation may reflect decreased neural efficiency and increased effort to attain the same performance as their non-maltreated peers. Notably, these findings are in line with the neuroimaging clinical literature of several disorders associated with maltreatment, such as anxiety (Basten, Stelzel and Fiebach, 2011), depression (Harvey, et al., 2005) and ADHD (Cortese, et al., 2012).

Summary. To date, two fMRI studies have investigated executive control in maltreated youth (Lim, et al., 2015; Mueller, et al., 2010). Both studies identified a pattern of increased brain activation in regions involved in executive functions such as inhibition and performance monitoring/updating, including the dACC/MCC and the fronto-lateral cortex. These findings, in conjunction with the clinical neuroimaging literature, suggest that neurocognitive alterations in executive control may increase the risk of mental health problems. However, a recent study by Danese and colleagues (Danese, et al., 2017) suggests that we should be cautious in assuming a causal link between maltreatment experience and alterations in executive function, as these may instead result from the socio-economic and genetic factors that commonly co-occur with maltreatment. Indeed, similar limitations may apply to the other neurocognitive domains of interests. However, to the best of our knowledge, this has not yet been investigated in population-representative birth cohort samples.

Conclusions: clinical implications

The functional neuroimaging literature suggests that the experience of abuse and neglect can influence the development of specific aspects of cognitive and affective functioning, which may increase vulnerability to future mental health problems. However, there are still common methodological shortcomings that characterise the neuroimaging literature of maltreatment that need to be addressed in future research if stronger causal inferences are to be made. Some of the most common limitations include small sample sizes, the lack of prospective/longitudinal designs and the conflation of severe maltreatment experience with adversity in the normal range. Moreover, it is essential that future studies aim to control for relevant confounding variables, such as IQ, pubertal status, age, gender, socio-economic status and the presence of mental health disorders, which are known to co-occur with the experience of maltreatment (see McCrory, Gerin and Viding [2017]) for a more comprehensive critique of these methodological concerns). Despite these limitations, the emerging pattern of findings reviewed here complements and extends those from wider psychological research, indicating, for example, increased hypervigilance and compromised emotion regulation skills in maltreated children (Curtis and Cicchetti, 2013; Kim-Spoon, Cicchetti and Rogosch, 2013; Romens and Pollak, 2012).

From a clinical perspective, two aspects of the findings we have reviewed merit particular attention. First, maltreatment-related changes resemble the neurocognitive profile associated with mental health disorders commonly associated with maltreatment, such as anxiety and depression. Second, these alterations are already present before a manifest clinical disorder. As such, they can be considered markers of latent psychiatric vulnerability since they may have prognostic value, but do not reflect overt symptomatology. Another important implication emerging from these findings is that, despite the link with mental health problems, these neurocognitive changes should not be readily interpreted as a sign of ‘damage’. Rather, in line with the theory of latent vulnerability (McCrory and Viding, 2015; McCrory, Gerin and Viding, 2017), they may in many instances be understood as the outcome of a complex set of adaptive processes which may confer short-term advantages for the child in the context of abusive and neglectful environments. However, they may equally incur long-term costs as an individual may not be equipped to deal with more normative challenges.

The neurobiological and psychological alterations which can follow experiences of maltreatment can be understood to increase mental health risk, particularly following exposure to future stressors, in both direct and indirect ways (McCrory, Gerin and Viding, 2017). Alterations in the way we process our internal and external worlds can have immediate repercussions: this can be understood as the direct effects of latent vulnerability. An example is the established pattern of hypervigilance to threat cues. While helpful to the child in a chaotic or dangerous home environment, such a response may curtail attentional resources available for the processing of other potentially helpful environmental cues, limiting the opportunities for learning and developing other cognitive and affective functions. Heightened response of the threat system may also lead to increased stress reactivity and experience of negative emotions – in other words, it serves to potentiate the negative impact of new stressor experiences. In this way, adaptation of the threat system may have ‘real-time’ implications for how the child negotiates their experience inside and outside the home.

In parallel, there are likely to be indirect effects that over time can compromise psychological and social functioning. Alterations of the threat system may undermine a child’s ability to develop positive peer friendships and social support networks that may help buffer their experience of future stressors. It may also lead them to act in ways that increase the likelihood of future stressor exposure, for example, owing to relationship breakdown or exclusion from school. This may unfold because heightened threat reactivity serves to increase the likelihood of misinterpreting ambiguous cues and over-responding to negative ones in ways that lead to more conflictual interactions. Equally, avoidance of threat or aversive cues (both internal and external) via dissociation and cognitive and behavioural strategies, while reducing distress in the short term, may impair the development of important skills, such as the effective detection of threat, in the longer term (e.g. DePrince, 2005).

When and how to intervene?

Currently (notwithstanding some exceptions), statutory interventions happen mainly at two stages. Once the maltreatment has been substantiated, professionals seek to ensure safety and the stability of the child’s placement. Then, if an individual meets clinical criteria for a mental health problem, they may be offered treatment from mental health services. However, extant neuroimaging findings are beginning to show that neuro-cognitive vulnerabilities are present before manifest behavioural symptoms emerge. These findings, alongside those indicating a variety of other psychological mediators between maltreatment and mental health difficulty, provide the motivation and the rationale to pursue a preventative care approach. In other words, help could be provided proximate to the detection of maltreatment experience to those most at risk of a worsening mental health trajectory.

Therefore, the natural next step would be to seek to develop a psychometric tool designed to screen for latent vulnerability that could help, as part of a formal assessment process, identify those children at most risk for later poor outcomes. However, the degree to which the extant neuroscience findings can shed light on models of prevention and intervention is much less clear; our view is that the field has not matured to this point. Rather, in the medium term we would hope that systematic neurocognitive research could help identify specific mechanisms that could be targeted in treatment. Further work is required, particularly within a longitudinal framework, in order to investigate the degree to which alterations of the systems reviewed here are implicated in the pathways to overt mental health problems and, furthermore, whether they are amenable to change. Such targeted mechanistic approaches are necessary given that ‘treatments as usual’ (Nanni, Uher and Danese, 2012) and general parental caring (Rothman and Silverman, 2007) may not be enough to prevent and ameliorate symptoms among individuals who have suffered early abuse and neglect. If we are able to accurately delineate which neurocognitive systems are altered following maltreatment, an important next question is how to promote adaptive change in these systems or compensatory protective neurocognitive functions which can foster resilience (McCrory, Gerin and Viding, 2017).

Future studies should systematically investigate the impact of a variety of positive relationships (involving peers, carers and others) and what factors promote the child’s ability to learn from these. Positive, predictable and safe relationships may help shift the child’s expectations of other people and build a foundation of trust. Repeated interactions within such relationships might create the conditions that could facilitate recalibration of the threat and reward processing systems. Alternatively, such relationships could foster development of compensatory strategies that counteract the affective processing biases. However, engaging in a positive, warm, consistent and constructive way with children who have experienced maltreatment can be challenging to their carers. If a child is hypervigilant to threat, less sensitive to reward, and has fewer emotion regulation and executive functioning skills, this can often evoke negative feelings and a sense of inadequacy in those who are trying to meet their needs. We argue that a more comprehensive understanding of the neurocognitive impact of maltreatment can help clinicians and carers to reframe the child’s behaviour and develop strategies that are helpful in ‘unhooking’ them from maladaptive patterns of interaction. Building positive peer cultures and harnessing the potential of digital technology are also important areas for future research and innovation. In relation to technology, certain apps can support self-reflection and emotion regulation, and can enable connections with supportive peers and others; this is especially useful if young people are experiencing isolation or ostracism elsewhere (McGeeney and Hanson, 2017).

One key factor that may be important in fostering recalibration of the neurocognitive systems impacted by maltreatment through relational experiences is the development of epistemic trust. This is the ability to use others to acquire new knowledge about the internal and external world – a capacity that has typically been compromised during maltreatment (i.e. the child comes to mistrust information from adults, closing down the ability to learn from others and the cultural world) (Fonagy and Allison, 2014). Children and adults privilege information from a trusted person in guiding their everyday interactions with others and participation in life. In other words, a foundation of epistemic trust with a caregiver can help promote positive interactions that facilitate the acquisition of new knowledge. In developing such carer- and peer-group approaches, it may be useful to draw on the knowledge surrounding a variety of evidence-based interpersonally focused therapies that apply an understanding of epistemic trust.

There are also other promising approaches that more directly target some of the neurocognitive alterations reviewed in this article. For example, DePrince and colleagues (2015) found that a 12-session ‘risk detection/executive functioning’ group intervention with maltreated adolescents, which included teaching mindfulness, problem-solving and accurate threat detection, led to a nearly five-fold decrease in reports of sexual victimisation in the following six months. It will be important to establish what precise neurocognitive mechanisms underpinned the improved outcome for the maltreated adolescents with this approach. More broadly, it may be fruitful to review techniques and approaches that have been developed in the context of treatment for manifest disorders and consider how these might be adopted or incorporated within a preventive model designed to enhance resilience. Dialectical Behavioural Therapy (DBT) for example, comprises a number of elements addressing emotion regulation, tolerating distress and improving interpersonal skills that may be extremely useful to consider.

As a final note, the ethical implications of any preventive strategy must be carefully considered in order to minimise risk of stigmatisation. How will deviation from normative development be explained and understood? How will individuals (who have been exposed to abuse and neglect) be screened? And how will they be engaged as active partners in any process of seeking and receiving support or help? Should this help be framed as promoting a resilient outcome? These, and other important issues, will require collaborative engagement with the young people and their families as active participants and careful consideration by professionals. In our view, such a collaborative approach has a greater chance of not only being more ethically grounded, but also of having greater efficacy in enabling and promoting agency and empowerment.

In summary, the acquisition of specific knowledge regarding neurocognitive processes impacted by early adverse experiences can help us understand how children who have been maltreated see the world around them and why they are often more vulnerable to developing mental health problems. In the longer term, this knowledge can inform the development of both a screening tool to identify those at most high risk and preventive approaches that effectively promote resilience and increase the likelihood of positive outcomes following childhood maltreatment.

Footnotes

Mattia I Gerin is a PhD student in the Developmental Risk and Resilience Unit (DRRU) in the Psychology and Language Sciences Department, University College London.

Elly Hanson is an independent clinical psychologist who specialises in the field of abuse and trauma.

Essi Viding is Professor of Developmental Psychopathology at University College London in the Faculty of Brain Sciences, where she co-directs the Developmental Risk and Resilience Unit.

Eamon J McCrory is Professor of Neuroscience and Developmental Psychopathology at University College London where he co-directs the Developmental Risk and Resilience Unit. He is also a Consultant Clinical Psychologist and Director of Postgraduate Studies at the Anna Freud National Centre for Children and Families, London.

References

Admon

Lubin

Stern

, et al. (2009) Human vulnerability to stress depends on amygdala’s predisposition and hippocampal plasticity. Proceedings of the National Academy of Sciences of the United States of America 106(33): 14120–14125. doi: 10.1073/pnas.0903183106

Admon

Milad

Hendler

(2013) A causal model of post-traumatic stress disorder: disentangling predisposed from acquired neural abnormalities. Trends in Cognitive Sciences 17(7): 337–347. doi: 10.1016/j.tics.2013.05.005

Balodis

Potenza

(2015) Anticipatory reward processing in addicted populations: a focus on the monetary incentive delay task. Biological Psychiatry 77(5): 434–444. doi: 10.1016/j.biopsych.2014.08.020

Basten

Stelzel

Fiebach

(2011) Trait anxiety modulates the neural efficiency of inhibitory control. Journal of Cognitive Neuroscience 23(10): 3132–3145. doi: 10.1162/jocn_a_00003

Caldji

Diorio

Meaney

(2003) Variations in maternal care alter GABA(A) receptor subunit expression in brain regions associated with fear. Neuropsychopharmacology 28(11): 1950–1959. doi: 10.1038/sj.npp.1300237

Clithero

Rangel

(2013) Informatic parcellation of the network involved in the computation of subjective value. Social Cognitive and Affective Neuroscience 9(9): 1289–1302. doi: 10.1093/scan/nst106

Coelho

Viola

Walss-Bass

, et al. (2014) Childhood maltreatment and inflammatory markers: a systematic review. Acta Psychiatrica Scandinavica 129(3): 180–192. doi: 10.1111/acps.12217

Cortese

Kelly

Chabernaud

, et al. (2012) Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI sudies. American Journal of Psychiatry 169(10): 1038–1055. doi: 10.1176/appi.ajp.2012.11101521

Curtis

Cicchetti

(2013) Affective facial expression processing in 15-month-old infants who have experienced maltreatment: an event-related potential study. Child maltreatment 18(3): 140–154. doi: 10.1177/1077559513487944

10.

Danese

Moffitt

Arseneault

, et al. (2017) The origins of cognitive deficits in victimized children: implications for neuroscientists and clinicians. American Journal of Psychiatry 174(4): 349–361. doi: 10.1176/appi.ajp.2016.16030333

11.

Dannlowski

Stuhrmann

Beutelmann

, et al. (2012) Limbic scars: long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Biological Psychiatry 71(4): 286–293. doi: 10.1016/j.biopsych.2011.10.021

12.

Dennison

Sheridan

Busso

, et al. (2016) Neurobehavioral markers of resilience to depression amongst adolescents exposed to child abuse. Journal of Abnormal Psychology 125(8): 1201–1212. doi: 10.1037/abn0000215

13.

DePrince

(2005) Social cognition and revictimization risk. Journal of Trauma & Dissociation 6(1): 125–141. doi: 10.1300/J229v06n01_08

14.

DePrince

Chu

Labus

, et al. (2015) Testing two approaches to revictimization prevention among adolescent girls in the child welfare system. Journal of Adolescent Health 56(2): S33–S39. doi: 10.1016/j.jadohealth.2014.06.022

15.

Eisenberg

Spinrad

(2004) Emotion-related regulation: sharpening the definition. Child Development 75(2): 334–339. doi: 10.1111/j.1467-8624.2004.00674.x

16.

Elsey

Coates

Lacadie

, et al. (2015) Childhood trauma and neural responses to personalized stress, favorite-food and neutral-relaxing cues in adolescents. Neuropsychopharmacology 40(7): 1580–1589. doi: 10.1038/npp.2015.6

17.

Etkin

Wager

(2007) Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry 164(10): 1476–1488. doi: 10.1176/appi.ajp.2007.07030504

18.

Etkin

Büchel

Gross

(2015) The neural bases of emotion regulation. Nature Reviews Neuroscience 16(11): 693–700. doi: 10.1038/nrn4044

19.

Evans

Kouros

Samanez-Larkin

, et al. (2015) Concurrent and short-term prospective relations among neurocognitive functioning, coping, and depressive symptoms in youth. Journal of Clinical Child and Adolescent Psychology 45(1): 6–20. doi: 10.1080/15374416.2014.982282

20.

Feiring

Cleland

(2007) Childhood sexual abuse and abuse-specific attributions of blame over six years following discovery. Child Abuse & Neglect 31(11–12): 1169–86. doi: 10.1016/j.chiabu.2007.03.020

21.

Folk

Zeman

Poon

, et al. (2014) A longitudinal examination of emotion regulation: pathways to anxiety and depressive symptoms in urban minority youth. Child and Adolescent Mental Health 19(4): 243–250. doi: 10.1111/camh.12058

22.

Forbes

Dahl

(2012) Research Review: Altered reward function in adolescent depression: what, when and how? Journal of Child Psychology and Psychiatry 53(1): 3–15. doi: 10.1111/j.1469-7610.2011.02477.x

23.

Gee

Gabard-Durnam

Flannery

, et al. (2013) Early developmental emergence of human amygdala – prefrontal connectivity after maternal deprivation. Proceedings of the National Academy of Sciences of the United States of America 110(39): 15638–15643. doi: 10.1073/pnas.1307893110/-/DCSupplemental.www.pnas.org/cgi/doi/10.1073/pnas.1307893110

24.

Gerin

Puetz

Blair

RJR

, et al. (2017) A neurocomputational investigation of reinforcement-based decision making as a candidate latent vulnerability mechanism in maltreated children. Development and Psychopathology 29(5): 1689–1705. doi: 10.1017/S095457941700133X

25.

Gilbert

Widom

Browne

, et al. (2009) Burden and consequences of child maltreatment in high-income countries. Lancet 373(9657): 68–81. doi: 10.1016/S0140-6736(08)61706-7

26.

Goff

Gee

Telzer

, et al. (2013) Reduced nucleus accumbens reactivity and adolescent depression following early-life stress. Neuroscience 249: 129–138. doi: 10.1016/j.neuroscience.2012.12.010

27.

Gotlib

Hamilton

Cooney

, et al. (2010) Neural processing of reward and loss in girls at risk for major depression. Archives of General Psychiatry 67(4): 380–387. doi: 10.1001/archgenpsychiatry.2010.13

28.

Green

McLaughlin

Berglund

, et al. (2010) Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: Associations with first onset of DSM-IV disorders. Archives of General Psychiatry 67(2): 113–123. doi: 10.1001/archgenpsychiatry.2009.186

29.

Gyurak

Gross

Etkin

(2011) Explicit and implicit emotion regulation: a dual-process framework. Cognition & Emotion 25(3): 400–412. doi: 10.1080/02699931.2010.544160

30.

Hanson

(2016) Understanding and preventing re-victimisation. In: Smith L (ed.) Clinical Practice at the Edge of Care. Cham: Springer International Publishing, pp. 197–227. doi: 10.1007/978-3-319-43570-1_10

31.

Hanson

Hariri

Williamson

(2015) Blunted ventral striatum development in adolescence reflects emotional neglect and predicts depressive symptoms. Biological Psychiatry 78(9): 598–605. doi: 10.1016/j.biopsych.2015.05.010

32.

Harvey

P-O

Fossati

Pochon

J-B

, et al. (2005) Cognitive control and brain resources in major depression: an fMRI study using the n-back task. NeuroImage 26(3): 860–869. doi: 10.1016/j.neuroimage.2005.02.048

33.

Hein

Monk

(2016) Research Review: Neural response to threat in children, adolescents, and adults after child maltreatment - a quantitative meta-analysis. Journal of Child Psychology and Psychiatry 58(3): 222–230. doi: 10.1111/jcpp.12651

34.

Kaplow

Dodge

Amaya-Jackson

, et al. (2005) Pathways to PTSD, Part II: Sexually abused children. American Journal of Psychiatry 162(7): 1305–1310. doi: 10.1176/appi.ajp.162.7.1305

35.

Karstoft

K-I

Armour

Elklit

, et al. (2015) The role of locus of control and coping style in predicting longitudinal PTSD-trajectories after combat exposure. Journal of Anxiety Disorders 32: 89–94. doi: 10.1016/j.janxdis.2015.03.007

36.

Kelly

Viding

Puetz

, et al. (2015) Sex differences in socioemotional functioning, attentional bias, and gray matter volume in maltreated children: a multilevel investigation. Development and Psychopathology 27(4): 1591–1609. doi: 10.1017/S0954579415000966

37.

Kerestes

Davey

Stephanou

, et al. (2014) Functional brain imaging studies of youth depression: a systematic review. NeuroImage: Clinical 4: 209–231. doi: 10.1016/j.nicl.2013.11.009

38.

Kim-Spoon

Cicchetti

Rogosch

(2013) A longitudinal study of emotion regulation, emotion lability-negativity, and internalizing symptomatology in maltreated and nonmaltreated children. Child Development 84(2): 512–527. doi: 10.1111/j.1467-8624.2012.01857.x

39.

Koenigsberg

Fan

Ochsner

, et al. (2010) Neural correlates of using distancing to regulate emotional responses to social situations. Neuropsychologia 48(6): 1813–1822. doi: 10.1016/j.neuropsychologia.2010.03.002

40.

LeDoux

(2000) Emotion circuits in the brain. Annual Review of Neuroscience 23: 155–184. doi: 10.1146/annurev.neuro.23.1.155

41.

Lee

Yoo

Kim

, et al. (2015) Aberrant function of frontoamygdala circuits in adolescents with previous verbal abuse experiences. Neuropsychologia 79: 76–85. doi: 10.1016/j.neuropsychologia.2015.10.029

42.

Lim

Hart

Mehta

, et al. (2015) Neural correlates of error processing in young people with a history of severe childhood abuse: an fMRI study. The American Journal of Psychiatry 172(9): 892–900. doi: 10.1176/appi.ajp.2015.14081042

43.

Maheu

Dozier

Guyer

, et al. (2010) A preliminary study of medial temporal lobe function in youths with a history of caregiver deprivation and emotional neglect. Cognitive, Affective & Behavioral Neuroscience 10(1): 34–49. doi: 10.3758/CABN.10.1.34

44.

Marusak

Martin

Etkin

, et al. (2015) Childhood trauma exposure disrupts the automatic regulation of emotional processing. Neuropsychopharmacology 40(5): 1250–1258. doi: 10.1038/npp.2014.311

45.

McCrory

Viding

(2015) The theory of latent vulnerability: reconceptualizing the link between childhood maltreatment and psychiatric disorder. Development and Psychopathology 27(2): 493–505. doi: 10.1017/S0954579415000115

46.

McCrory

De Brito

Sebastian

, et al. (2011) Heightened neural reactivity to threat in child victims of family violence. Current Biology 21(23): 947–948. doi: 10.1016/j.cub.2011.10.015

47.

McCrory

De Brito

Kelly

, et al. (2013) Amygdala activation in maltreated children during pre-attentive emotional processing. British Journal of Psychiatry 202(4): 269–276. doi: 10.1192/bjp.bp.112.116624

48.

McCrory

Gerin

Viding

(2017) Annual Research Review: Childhood maltreatment, latent vulnerability and the shift to preventative psychiatry – the contribution of functional brain imaging. Journal of Child Psychology and Psychiatry 58(4): 338–357. doi: 10.1111/jcpp.12713

49.

McGeeney

Hanson

(2017) Digital Romance: The centrality and affordances of technology in young people’s love lives. London: Brook and CEOP.

50.

McLaughlin

Peverill

Gold

, et al. (2015) Child maltreatment and neural systems underlying emotion regulation. Journal of the American Academy of Child and Adolescent Psychiatry 54(9): 753–762. doi: 10.1016/j.jaac.2015.06.010

51.

Meaney

(2001) Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience 24: 1161–1192. doi: 10.1146/annurev.neuro.24.1.1161

52.

Mehta

Gore-Langton

Golembo

, et al. (2010) Hyporesponsive reward anticipation in the basal ganglia following severe institutional deprivation early in life. Journal of Cognitive Neuroscience 22(10): 2316–2325. doi: 10.1162/jocn.2009.21394

53.

Mennin

Holaway

Fresco

, et al. (2007) Delineating components of emotion and its dysregulation in anxiety and mood psychopathology. Behavior Therapy 38(3): 284–302. doi: 10.1016/j.beth.2006.09.001

54.

Michl

McLaughlin

Shepherd

, et al. (2013) Rumination as a mechanism linking stressful life events to symptoms of depression and anxiety: longitudinal evidence in early adolescents and adults. Journal of Abnormal Psychology 122(2): 339–352. doi: 10.1037/a0031994

55.

Miyake

Friedman

Emerson

, et al. (2000) The unity and diversity of executive functions and their contributions to complex ‘Frontal Lobe’ tasks: a latent variable analysis. Cognitive Psychology 41(1): 49–100. doi: 10.1006/cogp.1999.0734

56.

Morgan

Olino

McMakin

, et al. (2013) Neural response to reward as a predictor of increases in depressive symptoms in adolescence. Neurobiology of Disease 52: 66–74. doi: 10.1016/j.nbd.2012.03.039

57.

Mueller

Maheu

Dozier

, et al. (2010) Early-life stress is associated with impairment in cognitive control in adolescence: an fMRI study. Neuropsychologia 48(10): 3037–3044. doi: 10.1016/j.neuropsychologia.2010.06.013

58.

Nanni

Uher

Danese

(2012) Childhood maltreatment predicts unfavorable course of illness and treatment outcomes in depression: a meta-analysis. The American Journal of Psychiatry 169(2): 141–151. doi: 10.1176/appi.ajp.2011.11020335

59.

O’Doherty

(2011) Contributions of the ventromedial prefrontal cortex to goal-directed action selection. Annals of the New York Academy of Sciences 1239(1): 118–129. doi: 10.1111/j.1749-6632.2011.06290.x

60.

Ochsner

Silvers

Buhle

(2012) Functional imaging studies of emotion regulation: a synthetic review and evolving model of the cognitive control of emotion. Annals of the New York Academy of Sciences 1251: E1–24. doi: 10.1111/j.1749-6632.2012.06751.x

61.

Parslow

Jorm

(2007) Pretrauma and posttrauma neurocognitive functioning and PTSD symptoms in a community sample of young adults. The American Journal of Psychiatry 164(3): 509–515. doi: 10.1176/ajp.2007.164.3.509

62.

Patel

Spreng

Shin

, et al. (2012) Neurocircuitry models of posttraumatic stress disorder and beyond: a meta-analysis of functional neuroimaging studies. Neuroscience and Biobehavioral Reviews 36(9): 2130–2142. doi: 10.1016/j.neubiorev.2012.06.003

63.

Pizzagalli

Holmes

Dillon

, et al. (2009) Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. The American Journal of Psychiatry 166(6): 702–710. doi: 10.1176/appi.ajp.2008.08081201

64.

Pollak

Sinha

(2002) Effects of early experience on children’s recognition of facial displays of emotion. Developmental Psychology 38(5): 784–791. Available at: www.ncbi.nlm.nih.gov/pubmed/12220055

65.

Pollak

Vardi

Putzer Bechner

, et al. (2005) Physically abused children’s regulation of attention in response to hostility. Child Development 76(5): 968–977. doi: 10.1111/j.1467-8624.2005.00890.x

66.

Puetz

Kohn

Dahmen

, et al. (2014) Neural response to social rejection in children with early separation experiences. Journal of the American Academy of Child and Adolescent Psychiatry 53(12): 1328–1337.e8. doi: 10.1016/j.jaac.2014.09.004

67.

Puetz

Viding

Palmer

, et al. (2016) Altered neural response to rejection-related words in children exposed to maltreatment. Journal of Child Psychology and Psychiatry and Allied Disciplines 57(10): 1165–1173. doi: 10.1111/jcpp.12595

68.

Puetz

Parker

Kohn

, et al. (2017) Altered brain network integrity after childhood maltreatment: a structural connectomic DTI-study. Human Brain Mapping 38(2): 855–868. doi: 10.1002/hbm.23423

69.

Radford

Corral

Bradley

, et al. (2011) Child Abuse and Neglect in the UK today: Research into the prevalence of child maltreatment in the United Kingdom. London: National Society for the Prevention of Cruelty to Children (NSPCC).

70.

Romens

Pollak

(2012) Emotion regulation predicts attention bias in maltreated children at-risk for depression. Journal of Child Psychology and Psychiatry 53(2): 120–127. doi: 10.1111/j.1469-7610.2011.02474.x

71.

Rosenblum

Coplan

Friedman

, et al. (1994) Adverse early experiences affect noradrenergic and serotonergic functioning in adult primates. Biological Psychiatry 35(4): 221–227. doi: 10.1016/0006-3223(94)91252-1

72.

Rothman

Silverman

(2007) The effect of a college sexual assault prevention program on first-year students’ victimization rates. Journal of American College Health 55(5): 283–290. doi: 10.3200/JACH.55.5.283-290

73.

Rutter

(2012) Resilience as a dynamic concept. Development and Psychopathology 24(2): 335–344. doi: 10.1017/S0954579412000028

74.

Shin

Liberzon

(2010) The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology  35(1): 169–191. doi: 10.1038/npp.2009.83

75.

Snyder

Miyake

Hankin

(2015) Advancing understanding of executive function impairments and psychopathology: bridging the gap between clinical and cognitive approaches. Frontiers in Psychology 6: 328. doi: 10.3389/fpsyg.2015.00328

76.

Snyder

Kaiser

Warren

, et al. (2015) Obsessive-compulsive disorder is associated with broad impairments in executive function: A meta-analysis. Clinical Psychological Science 3(2): 301–330. doi: 10.1177/2167702614534210

77.

Sripada

Angstadt

McNamara

, et al. (2011) Effects of alcohol on brain responses to social signals of threat in humans. Neuroimage 55(1): 371–380. doi: S1053-8119(10)01540-5 [pii]\r10.1016/j.neuroimage.2010.11.062

78.

Stringaris

Vidal-Ribas Belil

Artiges

, et al. (2015) The brain’s response to reward anticipation and depression in adolescence: dimensionality, specificity, and longitudinal predictions in a community-based sample. The American Journal of Psychiatry 172(12): 1215–23. doi: 10.1176/appi.ajp.2015.14101298

79.

Swartz

Knodt

Radtke

, et al. (2015) A neural biomarker of psychological vulnerability to future life stress. Neuron 85(3): 505–511. doi: 10.1016/j.neuron.2014.12.055

80.

Telzer

Fuligni

Lieberman

, et al. (2014) Neural sensitivity to eudaimonic and hedonic rewards differentially predict adolescent depressive symptoms over time. Proceedings of the National Academy of Sciences 111(18): 6600–6605. doi: 10.1073/pnas.1323014111

81.

Tottenham

Hare

Millner

, et al. (2011) Elevated amygdala response to faces following early deprivation. Developmental Science 14(2): 190–204. doi: 10.1111/j.1467-7687.2010.00971.x

82.

Ubl

Kuehner

Kirsch

, et al. (2015) Altered neural reward and loss processing and prediction error signalling in depression. Social Cognitive and Affective Neuroscience 10(8): 1102–12. doi: 10.1093/scan/nsu158

83.

Vachon

Krueger

Rogosch

, et al. (2015) Assessment of the harmful psychiatric and behavioral effects of different forms of child maltreatment. JAMA Psychiatry 55455(11): 1135–1142. doi: 10.1001/jamapsychiatry.2015.1792

84.

Viding

Sebastian

Dadds

, et al. (2012) Amygdala response to preattentive masked fear in children with conduct problems: the role of callous-unemotional traits. American Journal of Psychiatry 169(10): 1109–1116. doi: 10.1176/appi.ajp.2012.12020191

85.

White

Bogdan

Fisher

, et al. (2012) FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity. Genes, Brain, and Behavior 11(7): 869–78. doi: 10.1111/j.1601-183X.2012.00837.x

86.

White

Pope

Sinclair

, et al. (2013) Disrupted expected value and prediction error signaling in youths with disruptive behavior disorders during a passive avoidance task. American Journal of Psychiatry 170(3): 315–23. doi: 10.1176/appi.ajp.2012.12060840

87.

White

Tyler

Erway

, et al. (2016) Dysfunctional representation of expected value is associated with reinforcement-based decision-making deficits in adolescents with conduct problems. Journal of Child Psychology and Psychiatry 57(8): 938–946. doi: 10.1111/jcpp.12557

88.

Widom

DuMont

Czaja

(2007) A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up. Archives of General Psychiatry 64(1): 49–56. doi: 10.1001/archpsyc.64.1.49

89.

Wirtz

Hofmann

Riper

, et al. (2014) Emotion regulation predicts anxiety over a five-year interval: a cross-lagged panel analysis. Depression and Anxiety 31(1): 87–95. doi: 10.1002/da.22198

90.

Yates

Carlson

Egeland

(2008) A prospective study of child maltreatment and self-injurious behavior in a community sample. Development and Psychopathology 20(2): 651–71. doi: 10.1017/S0954579408000321

91.

Zhang

W-N

Chang

S-H

Guo

L-Y

, et al. (2013) The neural correlates of reward-related processing in major depressive disorder: a meta-analysis of functional magnetic resonance imaging studies. Journal of Affective Disorders 151(2): 531–9. doi: 10.1016/j.jad.2013.06.039