Developmental imaging genetics: challenges and promises for translational research

Advances in molecular biology, neuroimaging, genetic epidemiology, and developmental psychopathology have provided a unique opportunity to explore the interplay of genes, brain, and behavior within a translational research framework. Herein, we begin by outlining an experimental strategy by which genetic effects on brain function can be explored using neuroimaging, namely, imaging genetics. We next describe some major findings in imaging genetics to highlight the effectiveness of this strategy for delineating biological pathways and mechanisms by which individual differences in brain function emerge and potentially bias behavior and risk for psychiatric illness. We then discuss the importance of applying imaging genetics to the study of psychopathology within a developmental framework. By beginning to move toward a systems-level approach to understanding pathways to behavioral outcomes as they are expressed across development, it is anticipated that we will move closer to understanding the complexities of the specific mechanisms involved in the etiology of psychiatric disease. Despite the numerous challenges that lie ahead, we believe that developmental imaging genetics has potential to yield highly informative results that will ultimately translate into public health benefits. We attempt to set out guidelines and provide exemplars that may help in designing fruitful translational research applications that incorporate a developmental imaging genetics strategy

Initial Validation of a Brief Pictorial Measure of Caregiver Aggression: The Family Aggression Screening Tool

In the present study, we report on the development and initial psychometric properties of the Family Aggression Screening Tool (FAST). The FAST is a brief, self-report tool that makes use of pictorial representations to assess experiences of caregiver aggression, including direct victimization and exposure to intimate partner violence. It is freely available on request and takes under 5 minutes to complete. Psychometric properties of the FAST were investigated in a sample of 168 high-risk youth aged 16 to 24 years. For validation purposes, maltreatment history was assessed using the Childhood Trauma Questionnaire; levels of current psychiatric symptoms were also assessed. Internal consistency of the FAST was good. Convergent validity was supported by strong and discriminative associations with corresponding Childhood Trauma Questionnaire subscales. The FAST also correlated significantly with multi-informant reports of psychiatric symptomatology. Initial findings provide support for the reliability and validity of the FAST as a brief, pictorial screening tool of caregiver aggression

Annual Research Review: Childhood maltreatment, latent vulnerability and the shift to preventative psychiatry - the contribution of functional brain imaging

BACKGROUND: Childhood maltreatment is a potent predictor of poor mental health across the life span. We argue that there is a need to improve the understanding of the mechanisms that confer psychiatric vulnerability following maltreatment, if we are to progress from simply treating those with a manifest disorder, to developing effective preventative approaches that can help offset the likelihood that such disorders will emerge in the first place. METHODS: We review extant functional neuroimaging studies of children and adolescents exposed to early neglect and/or maltreatment, including physical, sexual and emotional abuse across four neurocognitive domains: threat processing, reward processing, emotion regulation and executive control. Findings are discussed in the context of 'latent vulnerability', where alterations in neurocognitive function are considered to carry adaptive value in early adverse caregiving environments but confer long-term risk. RESULTS: Studies on threat processing indicate heightened as well as depressed neural responsiveness in maltreated samples, particularly in the amygdala, thought to reflect threat hypervigilance and avoidance respectively. Studies on reward processing generally report blunted neural response to anticipation and receipt of rewards, particularly in the striatum, patterns associated with depressive symptomatology. Studies on emotion regulation report increased activation of the anterior cingulate cortex (ACC) during active emotion regulation, possibly reflecting greater effortful processing. Finally, studies of executive control report increased dorsal ACC activity during error monitoring and inhibition. CONCLUSIONS: An emerging body of work indicates that altered neurocognitive functioning following maltreatment: (a) is evident even in the absence of overt psychopathology; (b) is consistent with perturbations seen in individuals presenting with psychiatric disorder; (c) can predict future psychiatric symptomatology. These findings suggest that maltreatment leads to neurocognitive alterations that embed latent vulnerability to psychiatric disorder, establishing a compelling case for identifying those children at most risk and developing mechanistically informed models of preventative intervention. Such interventions should aim to offset the likelihood of any future psychiatric disorder

Investigating associations between empathy, morality and psychopathic personality traits in the general population

Although atypical moral and empathy processing are considered core features of psychopathic personality, little is known about how these constructs are associated with psychopathic traits in the general population. One-hundred and twenty-four adult males from the community were administered the Self-Report Psychopathy Scale 4 Short Form, as well as a wide battery of affect, empathy and morality tasks and questionnaires. Our findings indicate that both core affective-interpersonal, as well as lifestyle-antisocial features of psychopathy are associated with weaker empathic responses to fearful faces. However, only the unique variance of the affective-interpersonal features is associated with weaker empathic response to happy stories, lower propensity to feel empathic concern and less difficulty in making decisions on moral dilemmas. In contrast, the unique variance of the lifestyle-antisocial features is associated with greater propensity to feel empathic concern. These preliminary findings extend previous research and suggest that, while the joint variance between affective-interpersonal and lifestyle-antisocial features might drive some ‘deficits’ associated with psychopathy, there also appears also to be unique ‘deficits’ associated with the core affective-interpersonal features, particularly in relation to affective aspects of moral processing

Characterising youth with callous-unemotional traits and concurrent anxiety: evidence for a high-risk clinical group

Growing evidence supports the existence of two variants of youth with high callous-unemotional (CU) traits who present with markedly different risk profiles and outcomes, with potential implications for risk assessment and treatment formulation. So far, studies have identified variants of CU youth mainly using data-driven cluster approaches based on levels of CU traits and co-occurring anxiety. Yet, the extent to which this knowledge may be translated into clinical practice is unclear. To this end, the present study employed a severity-based, cut-off approach to systematically characterise CU groups across a range of clinically informative domains, including trauma history, psychiatric symptomatology, affective functioning, attachment style and behavioural risk. Analyses were based on multi-rated data from a community sample of high-risk youths (n = 155, M = 18 years). Consistent with previous studies, we found that, whereas variants show comparable levels of antisocial behaviour, those who present with both high CU and high anxiety report more severe childhood maltreatment, psychological distress, ADHD symptomatology and behavioural risk-including substance use, suicidal ideation and unsafe sex. In addition, these youth show greater attachment insecurity and affective dysregulation, as indexed by levels of irritability and alexithymia. Together, findings indicate that (1) trauma history is a key factor that differentiates variants of CU youth high vs. low on anxiety, and (2) differences in individual functioning across variants point to the need for tailored clinical assessment tools and intervention strategies. Importantly, the present findings indicate that variants of CU youth can be meaningfully differentiated using cut-off based approaches that parallel methods used in clinical assessments

Living with conduct problem youth: Family functioning and parental perceptions of their child

Parenting children with conduct problems (CP) is challenging, yet very little is known about the impact of the child’s behaviour on family functioning or how parents of children with CP perceive their child. The aim of this research was to examine whether families with children with CP and high vs. low levels of callous–unemotional traits (HCU vs. LCU) experience differences in family functioning and parental perceptions. One hundred and one parents/caregivers of boys aged 11–16 [Typically developing (TD) n = 31; CP/HCU n = 35; CP/LCU n = 35] completed the McMaster Family Assessment Device, measuring multiple domains of family functioning. Parents/caregivers also completed a written statement describing their child, used for qualitative analysis. Families with CP/HCU children had poorer affective involvement than TD (p = 0.00; d = − 1.17) and CP/LCU (p = 0.03; d = − 0.62) families. Families with CP/HCU children showed significantly poorer general family functioning (p = 0.04; d = − 0.63) and more poorly defined family roles (p = 0.005; d = − 0.82) than families with TD children. Qualitative analyses indicated that parents/caregivers of CP/HCU children characterised them as having a dichotomous personality and being superficially charming. CP/LCU children were characterised as cheeky and endearing, with parents reporting good rapport. Families with CP/HCU children presented with specific difficulties in affective involvement and parents described challenges which were in line with the child’s specific presentation of lack of empathy and shallow affect. These findings may be used to help clinicians identify targets for family interventions

Pathological Demand Avoidance (PDA): exploring the behavioural profile

‘Pathological Demand Avoidance’ is a term increasingly used by practitioners in the United Kingdom. It was coined to describe a profile of obsessive resistance to everyday demands and requests, with a tendency to resort to ‘socially manipulative’ behaviour, including outrageous or embarrassing acts. Pathological demand avoidance is thought to share aspects of social impairment with autism spectrum disorders, but autism spectrum disorder–appropriate strategies, such as routine and repetition, are described as unhelpful. Outrageous acts and lack of concern for their effects draw parallels with conduct problems and callous-unemotional traits. However, reward-based techniques, effective with conduct problems and callous-unemotional traits, seem not to work in pathological demand avoidance. Despite increasing interest and controversy over the pathological demand avoidance label, there is only one published study to date. We present the first systematic comparison of the behavioural profile of children receiving the term pathological demand avoidance (N = 25) to children with autism spectrum disorders (N = 39) or conduct problems and callous-unemotional traits (N = 28), using parent-report indices of psychopathology. The pathological demand avoidance group displayed comparable levels of autistic traits and peer problems to the autism spectrum disorders group and anti-social traits approaching those seen in the conduct problems and callous-unemotional traits group. Emotional symptoms in pathological demand avoidance exceeded both comparison groups. Findings highlight the extreme behavioural impairment associated with pathological demand avoidance and the need to explore whether behavioural overlap reflects a similar neurocognitive basis to existing groups

Modulation of amygdala response to task-irrelevant emotion

It has been shown that as cognitive demands of a non-emotional task increase, amygdala response to task-irrelevant emotional stimuli is reduced. However, it remains unclear whether effects are due to altered task demands, or altered perceptual input associated with task demands. Here, we present fMRI data from 20 adult males during a novel cognitive conflict task in which the requirement to scan emotional information was necessary for task performance and held constant across levels of cognitive conflict. Response to fearful facial expressions was attenuated under high (vs. low) conflict conditions, as indexed by both slower reaction times (RTs) and reduced right amygdala response. Psychophysiological interaction (PPI) analysis showed that increased amygdala response to fear in the low conflict condition was accompanied by increased functional coupling with middle frontal gyrus, a prefrontal region previously associated with emotion regulation during cognitive task performance. These data suggest that amygdala response to emotion is modulated as a function of task demands, even when perceptual inputs are closely matched across load conditions. PPI data also show that, in particular emotional contexts, increased functional coupling of amygdala with prefrontal cortex can paradoxically occur when executive demands are lower

Regional grey matter volume and concentration in at-risk adolescents: Untangling associations with callous-unemotional traits and conduct disorder symptoms

Structural Magnetic Resonance Imaging studies have reported volume reductions in several brain regions implicated in social cognition and emotion recognition in juvenile antisocial populations. However, it is unclear whether these structural abnormalities are specifically related to antisocial features, or to co-occurring callous-unemotional (CU) traits. The present study employed voxel-based morphometry to assess both grey matter volume (GMV) and grey matter concentration (GMC) in a large representative at-risk sample of adolescents (n=134; mean age 17.7 yr), characterized by a broad range of CU trait and conduct disorder (CD) symptom scores. There was a significant interaction between CD symptom and CU trait scores in the prediction of GMV in the anterior insula, with a significant positive association between CU traits and GMV in youth low on CD symptoms only. In addition, we found a significant unique positive association between CD symptoms and GMC in the amygdala, and unique negative associations between CU traits and GMC in the amygdala and insula. These findings are in line with accumulating evidence of distinct associations of CD symptoms and CU traits with amygdala and insula GMC in juvenile antisocial populations