Neurostructural correlates of normal and pathological dissociation

Normal, non-pathological dissociation is related to daydreaming and mind-wandering as well as altered affect and autobiographical memory. The contribution by Badura Brack and colleagues^{Reference Badura Brack, Marklin, Embury, Picci, Frenzel and Klanecky Earl11} investigated for the first time the neurostructural correlates of normal dissociation in a group of 180 children. They aimed to reveal neurostructural biomarkers of trait dissociation in healthy children while correcting for age, gender and traumatisation. Their results showed increased volume of the precuneus in children with higher levels of trait dissociation, which was not related to antecedent trauma exposure. Because of the pioneering nature of their research the authors discussed their finding in relation to neurofunctional correlates of both normal dissociation, that is mind-wandering, and pathological dissociation. Functional correlates of mind-wandering identified the importance of the precuneus/posterior cingulate cortex during this dissociative state, whereas the functional correlates of pathological dissociation included the posterior association areas. The authors therefore concluded that the precuneus is an essential brain region to consider in future dissociation research.

The precuneus was also implicated in a working memory study included in this themed series in individuals with a DID. Vissia and colleagues^{Reference Vissia, Lawrence, Chalavi, Giesen, Draijer and Nijenhuis12} acquired both behavioural data and neural activation patterns in 92 sessions during a working memory task. Genuine diagnosed DID and DID-simulating controls participated as authentic or simulated neutral and trauma-related identity states while a paired control group of individuals with PTSD and healthy controls participated as themselves. Identity state-dependent behavioural performance and neural activation were found, and DID simulators made fewer errors of omission than those with genuine DID. A second study^{Reference Reinders, Dimitrova, Schlumpf, Vissia, Nijenhuis and Jäncke13} in this themed series extended this sample of individuals with DID to address inconsistencies in findings regarding amygdala volume in relation to dissociation (see for review^{Reference Roydeva and Reinders1}). The study did not show differences in amygdala global and subregional volumes between the DID and the healthy control groups. A third study, by Daniels and colleagues,^{Reference Daniels, Mertens, Manthey, Sierk, de Jong and Walter14} further challenges the function of the amygdala in dissociative processing of trauma-related memories.

Trait and state dissociation

A unique study in individuals with a dissociative disorder not otherwise specified (DDNOS) used electroencephalography (EEG) of frontal brain regions to examine neural processing underlying acute dissociation. This study by Schäflein and colleagues^{Reference Schäflein, Mertens, Lejko, Beutler, Sattel and Sack15} is particularly interesting because it includes measures of both trait and state dissociation. This is important because little is known about how neurobiological processes are related to different dissociative symptoms (see for review^{Reference Roydeva and Reinders1}). Indeed, the study showed that experimentally elicited acute dissociation in people with DDNOS correlated positively with total EEG power at the beginning of a negative self-relevant condition but that this association was not present for trait dissociation. Despite the notes of caution and limitations of the study, the suggestion of the authors that their finding could serve as a brain biomarker for state dissociation is an important avenue to explore further.

Null finding in a script-driven imagery study

The involvement of frontal brain regions in pathological dissociation has been one of the most consistent findings transdiagnostically and independent of stimulus paradigm (see for review^{Reference Roydeva and Reinders1}). However, as highlighted in the paper by Mertens and colleagues,^{Reference Mertens, Manthey, Sierk, Walter and Daniels16} it remains important to corroborate results in independent samples. Their study used the script-driven imagery paradigm but did not confirm a priori hypothesised brain areas despite being one of the largest studies of its kind. Because of the relatively large sample and methodological rigour of the study we thought it important to publish this null finding in this themed series. A comment^{Reference Quide17} on this paper discusses possibilities to enhance neurobiological responses while keeping the script-driven imagery paradigm as the gold standard. One option provided was to integrate responsiveness of other biomarkers, such as physiological markers, with the neurofunctional markers. Analysing these biological responses to the script-driven imagery paradigm conjointly could increase response detection sensitivity. Additionally, we would like to propose implementing event-related designs presenting trauma-related words instead of scripts, which would allow for capturing short, transient neurofunctional responses.

Systematic reviews and meta-analyses: FND, genetics

This themed series also invited systematic reviews and meta-analyses. A review of dissociation and its biological and clinical associations in functional neurological disorder (FND) by Campbell and colleagues^{Reference Campbell, Smakowski, Rojas-Aguiluz, Goldstein, Cardeña and Nicholson18} might be perceived as controversial, because although FND is currently classified as a dissociative disorder in ICD-11, this conceptualisation is not widely accepted. The findings that dissociation in FND is associated with structural and functional brain alterations, including frontal brain regions, are clinically relevant and support the classification as a dissociative disorder.

The most deprived area of research in relation to dissociative symptoms is that of genetics. Fewer than 10 studies have investigated genetic biomarkers of dissociation and, owing to the lack of overlap in methodologies and samples, they are difficult to compare (see for review^{Reference Roydeva and Reinders1}). The most interesting study to date has been published in this themed series because Lee and colleagues^{Reference Lee, King, Li and Seng19} investigated gene–environment interactions with childhood maltreatment and dissociative symptoms in a trauma-exposed sample with or without a diagnosis of PTSD. Two oxytocin receptor gene single nucleotide polymorphisms (SNPs) were found to be associated with dissociative symptoms but not with a diagnosis of PTSD. A third SNP was found to be associated with dissociative symptoms when interacting with early childhood traumatisation. Such studies encourage future research into the genetics of trauma-related dissociation.