Introduction

Bipolar disorder (BD) is a chronic mental illness with features of fluctuations in mood state and has a lifetime prevalence ranging between 0.1 and 2.4% (Grande et al. 2016; Rowland and Marwaha 2018). It is also one of the most disabling conditions, causing high days out of role and disability-adjusted life years (Alonso et al. 2011; He et al. 2020). Among patients, impairment crosses neurocognitive domains, including attention, verbal learning and memory, and executive functions had been noted (Solé et al. 2017). Although there is no specific intervention with pro-cognitive effects so far, multiple factors such as age, education level, illness duration, and clinical course are associated with the cognitive impairment (Mann-Wrobel et al. 2011; Tamura et al. 2021). Adverse childhood experiences are not uncommon in BD patients, and studies have revealed an association between childhood adversities and poor cognitive presentation among individuals (Poletti et al. 2014; Rokita et al. 2018). A previous study targeting major depression and BD patients also highlighted that cognitive impairment is especially observed in subjects exposed to great childhood adversities, indicating the importance of early experience in the cognitive functions in mood disorders (Poletti et al. 2017).

Exposure to childhood adversity has been noticed as a risk factor of poor health outcomes, including both physical and mental health (Hustedde 2021; Petruccelli et al. 2019; Sonu et al. 2019). Studies also suggested that childhood trauma experience and its impact on outcomes may differ between genders (** working memory-specific dysfunction using a transdiagnostic approach. Neuroimage Clin. 2021;31:102747." href="/article/10.1186/s40345-024-00335-w#ref-CR76" id="ref-link-section-d156332386e2803">2021). More specifically, in BD, poor working memory performance has been noted with a thinner prefrontal cortex and parietal cortices (Cho and Goghari 2020), functional abnormality in the dorsolateral prefrontal cortex (DLPFC) and ventromedial prefrontal cortex (VMPFC) (Saldarini et al. 2022), and attenuated neural activation in the prefrontal cortex and posterior parietal cortex (Townsend et al. 2010). In addition, functional Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which mediates the degradation of dopamine, may also influence the aberrant activity of DLPFC during working memory performance in BD (Miskowiak et al. 2017). On the other hand, a study investigating post-institutionalized Romanian orphans showed that early deprivation with neglect could cause metabolism changes in many brain regions, including the orbital frontal gyrus, infra-limbic prefrontal cortex, medial temporal structures, lateral temporal cortex, and brain stem (Chugani et al. 2001). A study specifically focused on BD also showed that both physical and emotional neglect are associated with a dysregulated frontoparietal circuit, and physical neglect may specifically impact the functional connectivity of the left-caudate-seed to the frontoparietal network (Hsieh et al. 2021). Therefore, we notified that the brain network involved in subjects with childhood neglect corresponds to the brain area for working memory in BD. Furthermore, research has suggested that in a deprived early environment, there may be excessive synaptic pruning and problems with myelination, causing reductions in cortical thickness and white matter integrity (McLaughlin et al. 2017). In addition, other mechanisms also link early life stress to cognitive outcomes, including interaction with genotypes, epigenetic modification, behavioral adaptation, and the impact on the HPA axis, immune system, oxidative stress, and alteration in neurotrophin factors (Aas et al. 2019; Deighton et al. 2018; Grillault Laroche et al. 2020; Horn et al. 2019; Jaworska-Andryszewska and Rybakowski 2019; Jiang et al. 2019; Maes et al. 2022; Tyrka et al. 2013).

It is interesting to note that in this study, the multi-trauma cluster unexpectedly did not show the worst cognitive performance. These findings indicated that the impact of adverse childhood experience on cognition does not simply rely on the cumulative effect of different childhood traumas, and some cluster characteristics need to be mentioned. For example, in the current study, we excluded BD patients with substance use disorder, and the cluster with multi-trauma showed trend of older onset age, fewer total episodes, and shorter duration of the illness. Those who could remain stable could be a special subpopulation in this multi-trauma cluster, which may be protected from some other biological or psychological factors. For example, they could have larger gray and whiter matter volume in the hippocampus and greater connectivity between the central executive network and the limbic regions, as shown in the population with resilience remaining after exposure to childhood maltreatment (Moreno-López et al. 2020).

With a clustering method instead of a categorical method, the current study provides further understanding of common distributions of childhood trauma experience in BD and the unique profile of their cognitive performance. The results allowed us to evaluate the impact of a certain combination of childhood trauma subtypes and provided a more realistic point of view. But there are several limitations that should be considered in this study. First, childhood trauma experience was assessed via self-report, which inevitably faces the issue of recall bias and is often questioned for the possible influence of patients’ psychopathology. However, CTQ scales have proven validity and reliability in both psychotic patients (Fisher et al. 2011) and a BD population (Hosang et al. 2023). Second, more detailed information is lacking about the childhood trauma, such as the actual frequency and duration, which may lead to an over-simplified model for the understanding of trauma experience. Third, all of the participants were recruited from a single tertiary psychiatric hospital. Therefore, the patients likely had a more severe degree of illness and cognitive dysfunction, causing uncertainty about generalizability of the study. Fourth, the sample size in our study was small, leading to limited sizes for each cluster. Only 10% of the patients clustered into the multi-trauma group, making it difficult to demonstrate differences in performance of cognitive domains due to small sample size. A larger sample size of multi-trauma cluster might reveal a cognitive profile different from both low trauma cluster and neglect-focused trauma cluster. Fifth, while assessing cognitive performances, it’s important to consider the impact of medications. However, the effects of different categories of pharmacological treatment on cognitive deficits in BD have shown mixed results in previous studies (Sanches et al. 2015; Wingo et al. 2009; Xu et al. 2020; Yatham et al. 2017). Although there was no significant difference in psychotropic DDD between clusters, we noted a relatively low proportion of subjects receiving lithium treatment in the neglect-focus group, while the long-term beneficial effect of lithium to BD on their cognition compared with other anticonvulsants still needed more research for precise conclusions (Sabater et al. 2016). Lastly, we did not have longitudinal cognitive profiles to ensure the cognitive stability of the patients.

In conclusion, this study confirmed that neglect-focused trauma experience in BD may cause a negative impact on working memory function. There might be a unique influence of the neglect cluster over childhood abuse. Findings from this study suggest that in clinical practice, history of childhood trauma experiences, not only abuse but also neglect, should be assessed in BD population as it may be associated with cognitive deficits and require further attention while managing the patients. Further research is warranted for understanding the linking mechanisms of childhood neglect, such as disturbed neurodevelopmental process, neurocircuits, immune and inflammatory system. Specific interventions focusing on preventing cognitive deterioration are also required in this cluster of patients.