We investigated the influence of childhood trauma on the clinical symptoms of females with BD and the mediating role of social support in this relationship. According to the results, females with BD showed higher levels of childhood trauma but lower levels of social support than female healthy controls. Further, we observed that experiencing more childhood trauma was associated with more severe clinical symptoms, including depression, anxiety, and insomnia. In addition, social support played a role in attenuating the negative effect of childhood trauma. This study inspired us that targeting social support among BD patients may be helpful in treating and managing of BD.
Traumatic life events are risk factors for BD, and having experienced childhood trauma can exert a lasting effect on mental health (46). Childhood trauma may modify stress reactivity as well as exert detrimental effects via stress reactivity and lead to more severe clinical outcomes (47). As a stressor, childhood trauma may be involved in the pathogenesis of BD via the following mechanisms: 1) altering the developmental progression of the brain; 2) systemic inflammation; 3) alterations in hypothalamic-pituitary-adrenal (HPA) axis function, and disturbance of corticotropin-releasing factor (CRF) neural systems; and 4) genetic influence (48). The sensitivity to trauma varies across developmental periods. It was found that the maximal sensitive periods of BD patients to child trauma are at the ages of 6 and 11 years (49). Moreover, during development and maturation in children and adolescents, the brain is highly sensitive to stress such as childhood trauma (50). It was found that childhood trauma was associated with several alterations in grey matter volume and white matter of BD patients including hippocampus, thalamus, amygdala, frontal cortex, corpus callosum and the prefronto-limbic connectivity, and this effect may be mediated by childhood trauma induced-stress (51). In addition, factors that influence the fetal development can further produce permanent changes in postnatal growth and development (52). Babineau et al. found that childhood maltreatment experienced by pregnant women with bipolar disorder can influence the development and health of the next generation. They also found that maternal mood may be a transmission pathway (53). It seems that childhood trauma can exert both prenatal and postnatal effects on development and health. Activation of inflammation and immune dysfunction are widely found in BD patients (54, 55). Inflammation may play a role in the relationship between childhood trauma and BD. One study reported that childhood trauma was associated with increased immune/inflammatory markers (such as IL-2, IL-17, IFN-γ, and TNF-α) in BD patients (56). Also, the authors found that inflammation may mediate the detrimental effect of childhood trauma on brain structure (56). Childhood trauma could induce adaptive alterations in HPA axis function and structure during development, which may further alter the susceptibility of HPA axis to stress and the function of corticotrophin-releasing hormone signaling in adulthood (57). Studies found that BD patients with childhood trauma showed increased long-term cortisol and cortisol turnover, and blunted cortisol responses (58). Childhood trauma could increase the risk for mental illness independently of genetic loading (59). However, genetic mechanisms are recognized to play a role in the association between childhood trauma and HPA axis (60). For example, in BD patients, childhood trauma was associated with decreased expression of HPA axis genes including NR3C1 and DGKH (61). It induced hypermethylation of HPA axis gene (NR3C1), thus regulating the cortisol stress reactivity and diurnal HPA function (62, 63). In addition, allele A of GABA A receptor subunit gamma2 (GABRG2) polymorphism rs211034 exerted a protective effect on cognitive function in bipolar depression, while childhood trauma could eliminate this positive effect (64). Other genetic variations involved in the influence of childhood trauma on BD include: brain-derived neurotrophic factor (BDNF) gene val66met genotype (65), serotonin (5-hydroxytryptamine, 5-HT) transporter-linked polymorphic region (5-HTTLPR) in *s carrier (66), toll-like receptors 2 (TLR2) rs3804099 TT genotype (67), CLOCK rs1801260*C carrier (68), and single nucleotide polymorphic gene variants (SNPs) in or near genes coding for calcium channel activity-related proteins (69).
In this study, females with BD showed higher levels of childhood trauma than healthy controls. Our result was consistent with the above proposed idea that childhood trauma produces deleterious effects and is related with BD. Previous studies reported that childhood trauma was associated with symptoms of BD. For instance, childhood trauma predicted depressive symptoms (70). Childhood trauma is a risk factor of multiple negative outcomes including high severity of mania, depression, and psychosis, high risk of comorbidity, rapid cycling, and suicide attempt, early onset of BD, and greater number of manic and depressive episodes (71, 72).
Social support can be interpreted as a person who is loved, cared for, esteemed, and participates in a network of mutual obligations (73). Social interactions among people are important, and supportive interaction is a protective factor against life stress (73, 74). Previously, some studies found that social support served as a mediator or moderator between stress and physical or psychological health (26, 75, 76). A high level of social support is able to buffer stress induced by life experiences (77). The Social Convoy Model provides a conceptual framework that social support provided by parents in early childhood yields a “secure base” and a “safe haven” when faced with stress in subsequent life (77). These suggested that social support exerts a positive effect on life stress, and this benefit is also prominent in female people (32). The mechanisms by which social support impacts health and well-being are unclear. However, the response to stress was found to be a potential target of social support. Studies found that women who received emotional support were associated with more minor physiological changes in cardiovascular reactivity (e.g. diastolic blood pressure, cardiac output) compared to the no-support condition during acute stress (78, 79). When faced with chronic stress, perceived social support was uniquely related to depression, anxiety, and stress symptoms (80).
Many factors mediate the role in the relationship between childhood trauma and clinical symptoms. Social support is one of these factors, and it could influence the mental status of parents (33). It was reported that Subjective social support was negatively correlated with psychotic symptoms (81). Mood and anxiety disorders, including major depressive disorder, bipolar Ⅰ disorder, generalized anxiety disorder, and social anxiety disorder, are all associated with social support (29). In patients with major depressive disorder, poor perceived social support was a sequential mediator of the relationship between childhood trauma and depression severity (82). The clinical course of bipolar disorder is also influenced by social support. In BD patients with low social support, a high rate of relapse and delayed remission or recovery (83, 84), a decrease in treatment response (28), and worse suicidal thoughts or facilitation of suicidal behaviors (85) were observed. These suggested that poorer social support was related to unfavorable outcomes in BD (27, 77).
Treatment strategies targeting social support may serve as effective ways to promote the relief of psychiatric symptoms and reduce caregiver burden (28). The efficacy of psychosocial interventions on psychological distress has been widely explored (86–89). These interventions mainly aim to provide information or education, psychosocial support, practical skills, and stress reduction. Mindfulness-based stress reduction (MBSR) program was effective in reducing psychological distress, involving the mechanism of improving social support (90). In addition, online programs which provide web platforms, online support groups and online forums could improve social support by increasing interpersonal contacts and professional communications (91). These digital health programs initially appeared to be effective for mental health conditions, even if more evidence is needed to support the effectiveness (92, 93). However, current interventions targeting social support are still relatively few, let alone those applied in the field of mental illness.
There are several limitations in this study. Firstly, the mediation analysis applied in this study predicts a longitudinal process. However, this is a cross-sectional study, and we could not unveil a causal relationship among childhood trauma, social support, and clinical symptoms of BD. The disease itself may also influence social support (29). Long-term follow-up studies are beneficial to validate the hypothesized model in this study. Secondly, although we used an age-matched clinical control group, this study is limited by the small sample size. Finally, the assessment of childhood trauma and social support of all participants was based on self-report, which may make the data we obtained somewhat subjective. Moreover, the mood state could influence the retrospective reports of childhood trauma (94). Therefore, there may be some bias in the data used in this study.