Article summary with Childhood maltreatment, latent vulnerability, and the shift to preventative psychiatry - the contribution of functional brain imaging by McCrory a.o. - 2017

What is this article about?

Experiencing childhood maltreatment, for example physical, sexual, emotional abuse and neglect is a predictor of poor mental health across the life span. It increases the risk on psychiatry disorders in childhood and in adulthood. However, there is a lack of understanding in how maltreatment alters the neurocognitive systems and how it leads to mental health problems. Thus, clinicians are not so well equipped to identify or help children who are at most risk of developing mental health problems. This gap in the literature resulted from different factors. First, research in the field of child mental health has mainly focused on finding a medical model that explains psychiatric disorders. However, this is not good, because this research is underpinned by the assumption that individuals who have the same diagnosis are comparable. This is incorrect: individuals with the same disorder, differ from each other. For example, in individuals who have experienced maltreatment and have a psychiatric disorder, differ from people without such a history. Psychiatric disorders in this group often develop earlier, and often the symptomatology is more severe. There is also a higher risk on comorbidity, and a disorder in this group is more likely to be persistent and recurrent. Often standard treatment also do not work as well for this group.  Thus, individuals who have experienced childhood maltreatment within a diagnostic category have specific ecophenotypes.

Another reason for why there is such a big gap in the literature, is that it is difficult to measure and define maltreatment. Children who experience maltreatment often experience more than one form of abuse or neglect. There are also individual differences in severity, frequency, and the age of onset. Therefore, research has neglected this research domain.

However, there is now a shift. Because of neuroimaging research, alternations in neurocognitive systems following maltreatment can be measured. This is done using functional magnetic resonance imaging (Fmri). Research groups are also increasing into the topic of maltreatment. These groups started to systematically study neurocognitive mechanisms which are associated with maltreatment.

What is the theory of latent vulnerability?

The theory of latent vulnerability is a theory about the link between childhood maltreatment and the associated risk on psychiatric disorders across the life span. This theory states that because of maltreatment, there are measurable changes in neurobiological systems. These changes are often adaptive within the early maladaptive context; so they help to adapt to the environment. However, these changes which can be functional for the maladaptive environment, may be ineffective for other, normative contexts. This may increase the vulnerability of the individual for future stressors. These adaptations or changes can occur in different levels. For example, young adults who have experienced childhood maltreatment showed altered patterns of epigenetic modulation in genes which are implicated in different physical and psychiatric disorders. For example, maltreatment subtypes have unique methylation patterns. For example, physical abuse leads to changes in stress regulation, fear response, heart rate regulation. Physical neglect leads to changes in lipoprotein metabolism, polyamine metabolism, and regulation of cholesterol efflux.

The indicators of latent vulnerability are characterized by three key features, namely:

1. The indicators are not directly symptoms of a future disorder. Instead, the indicators refer to cognitive processes or representations and associated patterns of neural activation that are implicated in the existence of a disorder. For example, decreased reward sensitivity may make someone more vulnerable to depression. However, being reward insensitive is not a symptom of depression.
2. The indicators are best to be indexed at a systems level. This means that latent vulnerability refers to a complex phenotype which can be seen as ‘maladaptive calibration’ in higher order systems which are important for socioemotional and cognitive functioning. It would be more reasonable to hypothesize that a limited but different set of candidate neurocognitive systems are altered in a way that increases or reduces the risk on psychopathology after having experienced maltreatment. This would be better, because there is heterogeneity of maladaptive outcomes of maltreatment experiences.
3. The indicators should be present before the existence of a psychiatric disorder, and they should help to predict future risk. Even if we know that latent vulnerability is present, this does not tell us anything about the timing of the onset. For example, the vulnerability could be present for months or years, but disorders may only come into play when there is stress. Thus, the emergence or existence of a psychiatric disorder can be seen as an interaction between latent vulnerability and stressor exposure.

How is functional magnetic resonance imaging used in the study of childhood maltreatment?

Functional studies can help us to understand psychological mechanisms better. The evidence gathered with functional studies have shown differences in four neurocognitive systems, namely threat processing, reward processing, emotion regulation, and executive control.

Threat processing

For humans to survive, it is necessary for them to detect threat and respond to aversive and potentially dangerous stimuli. Therefore, we have neurobiological and cognitive systems which are prioritized for this detection of threat. The neural system associated with this often operates outside awareness, so consciously. The amygdala seems to play a critical role in detecting salient stimuli, and particularly dangerous stimuli. The amygdala works together with the thalamus, the pulvinar nucleus, and the superior colliculus.

Thus, threat processing is important for survival. Therefore we can expect that when there are alterations in this system, that this may lead someone to develop maladaptive behaviors. This is visible in anxiety disorders, which are associated with both vigilance (even in dangerous environments), and avoidance (when threat is present, and when someone should not avoid, but instead allocate attention to the threat). Inappropriate hypervigilance costs resources, which should be used for other important functions. Studies have shown that being hyperresponsive to threat predicts future symptomatology or psychopathology. For example, higher amygdala activity before stress exposure can predict later psychiatric symptoms.

Studies of threat processing in children and adolescents with a history of maltreatment have shown that experiencing maltreatment is associated with long-term impairments in their threat-processing and fear-processing systems. These changes are visible as early as 15 months. Changes include preferential attention to threatening information, heightened neural response to negative stimuli, and enhanced perceptual ability for cues that are associated with danger, such as angry faces. Animals also show changes as a result of early adverse experiences (such as reduced maternal care).

Functional brain studies have shown that children who have experienced maltreatment show greater activation in subcortical regions such as the amygdala and hippocampus during threat processing. Other researchers have demonstrated higher amygdala response to threatening facial cues in children who are exposed to early institutional neglect. Other research has demonstrated the role of the anterior insula. In children who had been exposed to maltreatment, amygdala activity and anterior insula activity was heightened. Thus, it seems that altered threat reactivity is a candidate neurocognitive system which is altered after maltreatment.

Reward processing

Humans have to be able to process rewards. This helps us to successfully adapt to our environment, because if we anticipate rewards, we are motivated and show goal-directed behavior. Therefore, humans always seek out natural rewards and also learn which neutral stimuli predict rewards. This happens in a conscious as well as an unconscious manner. Reward processing consists of three components: liking, wanting, and learning. Each of these components reflect different psychological processes.

Alterations in reward processing are visible during different pathological disorders, such as depression, substance abuse, and anxiety. It has been shown that disrupted striatal response during reward anticipation predicts anhedonia. Also, reduced activation in the ventral striatum predicts clinical depression and anhedonia two years later. Alterations in this reward network are also associated with vulnerability.

Studies on Romanian adoptees have shown that these adoptees have disrupted neural responses during the anticipation of monetary rewards.

There have also been three studies that have looked into reward processing in individuals who have experienced maltreatment. This showed that emotional neglect was associated with disrupted striatal response during reward processing. This lowered activity is also associated with more depressive symptoms. Another study found that maltreatment experience was associated with reduced activation to reward cues in the striatum, and in other regions such as the orbitofrontal cortex and insula. Another study conducted on older adolescents who had experienced physical and/or sexual abuse found an increased BOLD response when viewing positive social stimuli compared to neutral social stimuli. Maltreatment seems to predict depressive symptoms only for youth who have lower reward reactivity both neurally and behaviourally. Thus, maltreatment predicts more depressive symptoms only for adolescents who have low activation of the left putamen in response to positive images. Having greater reactivity to rewards is a protective factor against depression for adolescents who have experienced maltreatment.

Emotion regulation

Emotions are difficult to define and therefore, emotion regulation is too. However, most researchers agree on that emotions are innate, and that they are adaptive. They help us to appraise our environment and prepare us for action. Emotions are seen as a complex neurophysiological phenomenon which help to evaluate our environment as well as change our motivational state and behaviour. Emotion regulation is defined as the ability to produce changes in emotions. Thus, it is used to change the valence of it (good or bad), and its intensity or duration. It is a dynamic and multifaceted process, and it can take place without conscious awareness.

Neuroimaging studies have shown interconnected circuits which are involved in emotion regulation. Especially subcortical or limbic regions are involved in the evaluation of threat, reward, and internal physiological states have been shown to be interconnected with frontal regions such as the anterior cingulate cortex (ACC). These regions are important for integrating information from different sensory modalities, and they are implicated in processes of successful emotion regulation. This involves assessing one’s own and others’ mental states, monitoring conflicting information, inhibiting and selecting behavioural responses and attributing context-dependent value to stimuli.

When people experience difficulties in emotion regulation, this is often associated with psychiatric disorders, such as anxiety, depression, conduct disorder, and substance abuse disorder. Also, alterations in emotion processing serve as a predictor for future psychiatric conditions and difficulties in social functioning. Studies in maltreated children show that differences in emotion regulation predict future psychopathology. For example, maltreatment experience has been shown to be associated with high emotion lability/negativity at the age of 7. This leads to poor emotion regulation, and this in turn predicts internalizing symptoms later. Thus, poor emotion regulation is involved in the development of internalizing problems, such as anxiety.

There have been multiple studies that have looked into the brain circuits that are involved in emotion regulation in children and adolescents with a history of maltreatment. These studies have shown that there is atypical focal brain activity in regulatory brain regions such as the ventral ACC (vACC) and the IPFC. Also, there are alterations in the connections between frontal and subcortical brain regions, such as the amygdala-vACC circuit. Studies into the functional connectivity between the amygdala and frontal regions have shown that there are differences in younger children’s functional coupling between the amygdala and mPFC when they viewed emotional faces. Another study has shown that, in a group of normative developing adolescents, that there is more negative functional connectivity between amygdala activity and the rostral ACC. This is associated with more verbal abuse and depressive symptoms. Another study found that a group of trauma-exposed children did not show a typical pattern of negative connectivity between the amygdala and the vACC. They differed from their peers.

Other studies have looked into brain activity in children with a history of maltreatment. Differences between this group and nonmaltreated children were mostly found in brain regions such as the ventral and dorsal ACC and the IPFC. Other studies found an overall increase activity in the dorsolateral PFC and also in the dorsal and ventral ACC.

Executive control

Executive control refers to planning, flexible thinking, and anticipating outcomes. This is really important, because this helps to accomplish day-to-day activities as well as long-term goals. There are three functions of executive control: updating, inhibiting, and task shifting. Updating refers to working memory, and is defined as manipulating and maintaining information in an active state (sustaining attention), and to disregard distracting inputs (attention control).

Inhibitory control is defined as the ability to constrain automatic or dominant behavioural and cognitive responses which are counterproductive. Shifting refers to the ability to switch between different mental tasks, mental states, and concepts. All three functions interact and are necessary for effective decision-making and adaptive behaviours such as self-regulation, and the ability to monitor performance and detect errors.

When people have disrupted executive control, this is associated with lower emotion regulation skills, more rumination, and reduced social skills. In turn, these are all predictors of psychopathology.

There have been two studies conducted using fMRI to find neural correlates of executive control in children and adolescents who have been exposed to maltreatment or institutionalization. These studies have shown that there is increased activity during error monitoring and inhibition in regions such as the medial and frontal motor regions. This may increase the risk on future psychopathology.

What are implications for future research?

There are five suggestions from these authors to enhance the validity of future studies, namely

1. Ensure effective matching. In studies that compare nonmaltreated children and adolescents to a control group, it is important to make sure that these groups are matched on age, IQ, sex, and SES;
2. All maltreatment domains should be characterized. Studies should be clear about which kinds of maltreatment their participants have experienced.
3. Do not conflate adversity in the normal range with maltreatment exposure. When a sample includes mostly typically developing children, then these findings can tell us about development as a result of normal adversity. But, they do not tell us a lot about actual maltreatment.
4. Take particular care in measuring emotional abuse using self-report instruments. When possible, researchers should try to use prospective and objective measures of maltreatment, such as institutional records.
5. Longitudinal designs. Longitudinal studies are necessary to determine whether alterations in neurocognitive functioning lead to future psychiatric disorders.