Childhood Trauma, Brain Structure and Emotion Recognition in Patients With Schizophrenia and Healthy Participants

Karolina I. Rokita; Laurena Holleran; Maria R. Dauvermann; David Mothersill; Jessica Holland; Laura Costello; Ruán Kane; Declan McKernan; Derek W. Morris; John P. Kelly; Aiden Corvin; Brian Hallahan; Colm McDonald; Gary Donohoe

Disclosures

Soc Cogn Affect Neurosci. 2020;15(12):1336-1350. 

In This Article

Discussion

In this study, we tested the hypothesis that the association between higher levels of childhood trauma and poorer emotion recognition would be mediated via reduced volumes in one or more of three stress-sensitive brain regions—the hippocampus, amygdala and/or ACC. We observed that the association between increased childhood trauma exposure (measured in terms of both physical neglect and total childhood trauma scores) and lower emotion recognition scores is mediated, at least partly, via reduced total and left ACC volumes in healthy participants. This was observed in the absence of similar associations with either the hippocampus or amygdala. To the best of our knowledge, this is the first study to evaluate a specific link between childhood trauma, brain structure and emotion recognition.

The Role of the ACC in the Association Between Childhood Trauma and Emotion Recognition

When examining the association between childhood trauma and the ROI volumes in the whole sample, we observed a significant negative association between physical neglect and the overall CTQ score, with the total ACC volumes. These results are consistent with previous studies reporting smaller ACC volumes in clinical and non-clinical populations following early life trauma (Dannlowski et al., 2012; Meng et al., 2014; Cancel et al., 2019). We also observed a significant positive association between emotion recognition and the total, left and right volumes of the ACC. Consistent with these findings, several studies have suggested that better ability to recognise emotions is associated with larger ACC volumes in both clinical and non-clinical populations (Fujiwara et al., 2007; Szymkowicz et al., 2016).

In terms of our main hypothesis that childhood trauma related effects on emotion recognition would be mediated by volumetric changes, reduced ACC volumes were observed to fully mediate the association between childhood trauma and emotion recognition in healthy participants. The role of the ACC region as a potential mediator in the relationship between childhood trauma and emotion recognition is novel and highlights the importance of this particular brain area in emotion processing.

There are a range of possible explanations for why variation of volume in the ACC may mediate the effects of childhood trauma on emotion recognition, including (i) the idea of a trauma-sensitive critical period for brain development, (ii) the role of the ACC in emotional awareness and (iii) the role of the ACC in detecting social exclusion. In terms of the notion that the ACC region may be more sensitive to adversity during development, some researchers (Do et al., 2009; Pizzagalli, 2011; Teicher et al., 2016) argue that there may be a 'critical period' for the normal development of anterior cortical areas, during which the impact of various stressors could be particularly detrimental. The PFC is a region with delayed ontogeny (Weinberger et al., 1986), and consequently may be affected more by environmental stressors than other brain areas, as shown in studies of animal models (Radley et al., 2006; Pascual and Zamora-Leon, 2007). Another possible explanation for a potential mediating role of the ACC is that this region is involved in emotional awareness and self-referential thinking essential for conscious self-monitoring, which in turn is important for adapting cognitively and socially to various experiences and being aware of the environment (Lou et al., 2017). Trauma-related alterations to ACC may impair these processes, affecting the ability to accurately identify emotional expressions. Further, ACC has also been shown to be a key region involved in the detection of social exclusion. Since humans are sensitive about being included by others, negative experiences associated with rejection (e.g. physical neglect) may affect the ability to effectively adapt to social environments by hindering monitoring or detection systems that are highly sensitive to social exclusion (Gauthier et al., 1996; Kawamoto et al., 2012; Garcia et al., 2016). The ACC region is in fact often implicated in physical and social pain research as disruption in ACC activity has been consistently demonstrated while experiencing physical as well as 'social pain', such as rejection, exclusion, humiliation or grief, based on previous studies and meta-analyses (Eisenberger et al., 2003; Eisenberger, 2015; Lieberman and Eisenberger, 2015; Rotge et al., 2015).

In regard to our clinical sample, we did not find the same mediating role of the ACC in patients. This was despite the fact that our patient sample showed higher rates of childhood trauma experiences (specifically physical neglect and total CTQ scores). Given the previously observed association between childhood trauma, structural brain alterations and poor social cognitive function in patients with SZ (Trémeau, 2006; Rokita et al., 2018, 2020; Cancel et al., 2019; Popovic et al., 2019), the lack of significant mediating effects in the patient group is surprising. One potential explanation for this difference between healthy participants and patients relates to the difference in sample size between these groups. While the patient group was relatively large for a sample of this size, it is difficult to calculate exactly what the power of a given sample is in mediation analysis. This, together with the known heterogeneity in patients with SZ, in terms of illness severity (Wolfers et al., 2018), brain structure (Zhang et al., 2014) and cognitive performance (Carruthers et al., 2019), may have prevented us from being able to detect indirect (mediating) associations, despite the high levels of childhood adversity reported.

The Role of the Amygdala and Hippocampus in the Association Between Childhood Trauma and Emotion Recognition

In terms of an association between childhood trauma and the other two ROIs in the whole sample, we did not observe significant associations between childhood trauma and amygdala volumes, contrary to findings from Aas et al. (2012) and Hoy et al. (2012). However, several meta-analyses showed inconsistent findings for the amygdala (McCrory et al., 2011; O'Doherty et al., 2015). In fact, volumetric changes of the amygdala are complex and likely to be moderated by the type and exposure timing of childhood trauma (Berens et al., 2017). We also did not observe significant associations between amygdala volume and the ability to recognise emotions. The importance of this brain region in emotion processing has been demonstrated primarily in functional MRI studies rather than structural imaging studies (Taylor et al., 2012; Spohrs et al., 2018; Zinchenko et al., 2018). Where changes in amygdala volume have been correlated with emotion recognition, these associations have been specific to negative facial expressions (e.g. fearful) (Zhao et al., 2013; Warnell et al., 2018), whereas our study examined the ability to recognise emotions more generally.

Similar to Aas et al. (2012), we did not find a significant association between childhood trauma and hippocampal volumes. However, we did observe a significant positive association between the ERT total score and the total, left and right volumes of the hippocampus, which is consistent with previous studies (Fujiwara et al., 2007; Szymkowicz et al., 2016). In terms of our mediation hypothesis, the hippocampus was not observed to mediate the effects of childhood trauma on emotion recognition in either group. The lack of mediating effects of the hippocampus may reflect the influence of other factors that were not examined in this study. For instance, school/workplace bullying and other stressful events in adulthood have also been associated with variations in hippocampal volume (Zannas et al., 2013; Nolfe et al., 2018).

Between-group Differences on ROI Volumes

When examining between-group differences on ROI volumes, we observed significant reductions of the total, left and right hippocampal volumes in patients compared to healthy participants. This is one of the most consistently reported findings in SZ. Numerous neuroimaging studies and meta-analyses have reported reduced hippocampal volumes in chronic patients as well as those with first-episode psychosis and ultra-high risk individuals (Wright et al., 2000; Sumich et al., 2002; Arnold et al., 2015; Dean et al., 2015; Ho et al., 2017; Lieberman et al., 2018). In terms of between-group differences on the amygdala and ACC volumes, no significant differences were reported. Considering the effect sizes reported for these differences by the ENIGMA Schizophrenia Working Group (van Erp et al., 2016), the non-significance of these differences is likely to reflect the limited power in the current sample.

Limitations

Although the findings of our study provide novel evidence for the detrimental effects of childhood trauma on emotion processing and structural brain measures of volume associated with emotion recognition deficits, some limitations should be mentioned. Firstly, the assessment of childhood trauma experiences was based on a retrospective self-report. Although the CTQ questionnaire is reported to provide reliable and valid screening of childhood maltreatment experiences (Bernstein et al., 1997), such measures are generally criticised for liability to recall bias. Based on our observations during testing, it appears that a number of participants, specifically patients, may have under-reported their early life traumatic experiences as feedback from some individuals seems to suggest that they felt uncomfortable disclosing childhood experiences. Such under-reporting of traumatic experiences may have impacted our ability to accurately measure the mediating effects of brain structure in relation to childhood trauma and emotion recognition. Several studies have suggested that patients with SZ are more likely to under-report instances of childhood maltreatment than healthy individuals for a variety of reasons, such as distrust towards researchers or other professionals, not feeling comfortable disclosing information on this sensitive topic or to avoid pain and embarrassment when verbalising and thinking about these experiences—the former is likely to be related to SZ symptoms (e.g. paranoia) (Fisher et al., 2009; McKinney et al., 2009). In future studies, the accuracy of childhood maltreatment measures might be aided by the use of additional sources, such as clinical documentation or family interviews, where possible. Secondly, because of a multiple testing burden, we did not include other brain regions involved in emotion recognition impairments in our analysis, for instance the insula or the fusiform face area, which are also relevant to understanding the relationship between childhood trauma and emotion recognition studied here. Thirdly, we did not assess other stressful life events, including traumatic experiences after the age of 18, which may also contribute to structural changes in several brain regions, including the hippocampus, amygdala and ACC (Papagni et al., 2011). Further, it is possible that larger samples of patients with SZ would yield more prominent findings, similar to those observed in the healthy group. Additionally, our study examined the effects of childhood trauma on brain structure and emotion recognition in a mixed patient sample consisting of individuals with SZ and those with a SZA. Further studies should examine this relationship in both groups separately to determine the possible differential outcomes. Lastly, we were unable to investigate the possible impact of childhood trauma duration and onset, which could contribute to the results as there may be sensitive periods when specific brain areas are most sensitive to stressful events (Dannlowski et al., 2012; Gee and Casey, 2015).

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