Structural connectomic signatures of childhood maltreatment across affective and psychotic disorders.

Childhood maltreatment and impaired emotion regulation and processing in remitted affective disorders: Evidence from a large-scale investigation.

Childhood maltreatment is an established risk factor for incident unipolar disorder and bipolar disorder. It is separately observed that affective disorders (AD) are also associated with higher nucleoside damage by oxidation. Childhood maltreatment may induce higher levels of nucleoside damage by oxidation and thus contribute to the development of AD; however, this relation is only sparsely investigated. In total, 860 participants (468 patients with AD, 151 unaffected first-degree relatives, and 241 healthy control persons) completed the Childhood Trauma Questionnaire (CTQ). The association between CTQ scores and markers of systemic DNA and RNA damage by oxidation as measured by urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) levels, respectively, was investigated. In multiple regression models adjusted for sex- and age, 8-oxodG and 8-oxoGuo levels were found to be higher in individuals who had experienced more childhood maltreatment. These associations persisted in models additionally adjusted for body mass index, alcohol, and current smoking status. Emotional abuse, sexual abuse, and emotional neglect were principally responsible for the foregoing associations. Our findings of an association between childhood maltreatment and oxidative stress markers suggest that childhood maltreatment overall, notably emotional abuse and emotional neglect, is associated with enhanced systemic damage to DNA and RNA in adulthood. Further, individuals with AD reported a higher prevalence of childhood maltreatment, which may induce higher levels of nucleoside damage by oxidation in adulthood, possibly leading to increased risk of developing AD. Longitudinal studies are needed to clarify this relationship further.

This study aimed to elucidate the contribution of childhood maltreatment (CM) and the disease of major depressive disorder (MDD) on cognitive function in medication-free patients in a current depressive episode, and to examine the effect of CM on the improvement of cognitive function after treatment with antidepressants. One hundred and fifty-three unmedicated patients with MDD and 142 healthy controls (HCs) underwent clinical interviews. CM assessment was performed using the Childhood Trauma Questionnaire (CTQ), and a battery of comprehensive neurocognitive tests was used to assess the participants' executive function, processing speed, attention, and memory. After 6months of treatment with antidepressants, the neurocognitive tests were reperformed in patients with MDD and HCs. There was a significant main effect of MDD on all four cognitive domains, while the main effect of CM was only significant on memory. No significant interactive effect was found between MDD and CM on any of the cognitive domains. In the MDD group, higher CTQ total score was predictive of poorer memory performance. After treatment, significant main effects of treatment and MDD were found on all four cognitive domains in remitted patients with MDD. No significant main effect of CM or three-way interaction effect of treatment × MDD × CM was found on any of the cognitive domains. The disease of MDD contributed to impairments in all four cognitive domains. CM independently contributed to memory impairment in patients in a current depressive episode, with higher severity of CM predictive of poorer memory performance.

Background: Extant research has provided evidence for disparities between patients with schizophrenia spectrum disorder (SSD) who have and have not experienced childhood maltreatment (CM) in terms of treatment outcome, psychopathology and their propensity to engage in offending behavior. However, research addressing all phenomena is scarce.Objective: The current study aims to explore differences between offender patients with SSD and CM and those with SSD and no CM in terms of their offending, psychopathology at different points in time and treatment outcome.Method: In the present explorative study, latent class analysis was used to analyze differences between 197 offender patients with SSD and CM and 173 offender patients with SSD and no CM, who were admitted to forensic psychiatric inpatient treatment between 1982 and 2016 in Switzerland.Results: Three distinct homogenous classes of patients were identified, two of which were probable to have experienced significant CM. One third of patients with SSD and CM were probable to benefit from inpatient treatment, even surpassing results observable in the group without CM, whereas the other group with SSD and CM was probable to benefit less. Patients with SSD and no CM displayed more psychopathology at first diagnosis and prior to their index offense. Interclass differences in offending behavior were minimal.Conclusions: Offender patients with SSD and CM differ not only from offender patients with SSD and no CM, but also amongst themselves. While some with SSD and CM experience a remission in psychopathology and improve their prognosis for future offending behavior, others do not. Directions for future research on SSD and CM are discussed.

Reduced fractional anisotropy (FA) associated with Major Depressive Disorder (MDD) overlaps anatomically with effects of childhood maltreatment experiences. The aim of this study was, therefore, to replicate the negative effect of childhood maltreatment on white matter fiber structure and to demonstrate, that alterations in MDD might be partially attributed to the higher occurrence of childhood maltreatment in MDD. Two independent cohorts (total N = 1 256) were investigated in a diffusion tensor imaging study: The Münster Neuroimaging Cohort (MNC, N = 186 MDD, N = 210 healthy controls, HC) as discovery sample and the Marburg-Münster Affective Disorders Cohort Study (MACS, N = 397 MDD, N = 462 HC) as replication sample. The effects of diagnosis (HC vs. MDD) and Childhood Trauma Questionnaire (CTQ) scores on FA were analyzed. A main effect of diagnosis with higher FA in MDD patients compared with HC was found in the MNC (pFWE = 0.021), but not in the MACS (pFWE = 0.52) before correcting for CTQ. A significant negative correlation of FA with CTQ emerged in both cohorts (MNC: pFWE = 0.006, MACS: pFWE = 0.012) in several tracts previously described in the literature. No CTQ × diagnosis interaction could be detected. Any main effect of diagnosis was abolished after correcting for CTQ (MNC: pFWE = 0.562, MACS: pFWE = 0.115). No differences in FA between MDD and HC could be found after correcting for childhood maltreatment, suggesting that previously reported group differences might be attributed partially to higher levels of maltreatment experiences in MDD rather than diagnosis itself. Furthermore, a well-established finding of reduced FA following childhood maltreatment experiences was replicated.

Childhood maltreatment has been linked to impairments in social functioning and social cognition in adults with affective disorders. However, conclusions have been limited by inconsistent findings across different maltreatment subtypes and social domains. We conducted a systematic review and meta-analysis to quantify associations between childhood maltreatment (overall and subtypes - physical, emotional and/or sexual abuse, and/or physical and/or emotional neglect) and different domains of social functioning and social cognition in adults with affective disorders (bipolar disorder or major depressive disorder). We also examined effect moderators and mediators of these associations. A systematic search was performed on 12.12.2022 which identified 29 studies included in qualitative synthesis (n = 3022 individuals with affective disorders), of which 27 (n = 2957) were pooled in meta-analyses. Across studies, five social functioning and five social cognition domains were examined, of which four domains of social functioning and two domains of social cognition had sufficient data for meta-analysis (PROSPERO CRD42022288976). Social functioning: childhood maltreatment was associated with lower global social functioning (r = -0.11 to -0.20), poorer interpersonal relations (r = -0.18 to -0.33), and with aggressive behaviour (r = 0.20-0.29) but was unrelated to vocational functioning. Emotional abuse and emotional neglect showed the largest magnitudes of effect. Social cognition: there was no meta-analytic evidence of associations between maltreatment and social cognition domains. Exploratory moderation analyses did not identify any consistent moderators. Narrative synthesis identified attachment style as possible moderator, and sensory patterns, anxiety, and depressive symptoms as possible mediators between childhood maltreatment and social outcomes. Overall, the available evidence was limited, particularly in relation to social cognition. Adults with affective disorders are at risk of social functioning difficulties after childhood maltreatment exposure, an effect observed across multiple maltreatment subtypes, social functioning domains, and diagnoses. Addressing social functioning problems may benefit maltreated adults with both bipolar disorder and major depressive disorder.

Childhood maltreatment (CM) is closely linked to internet addiction (IA), especially in adolescents with Major Depressive Disorder (MDD). Previous studies have shown that adolescents who experience CM are more likely to develop IA and other psychological problems. This study aims to explore the complex relationship between CM and IA through network analysis, particularly identifying the core symptoms and bridge symptoms to better understand the development of IA in these adolescents. A cross-sectional study was conducted in seven hospitals in Anhui Province, China, involving 332 adolescents diagnosed with MDD using DSM-5 criteria. The Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Internet Addiction Test (IAT) were used to assess CM and IA symptoms, respectively. Gender-based network analysis was also performed. Network analysis constructed a CM-IA network and identified core and bridge symptoms. "Depress/moody/nervous being offline", "Request an extension for longer time", "Sleep loss due to late-night logins", and "emotional abuse" emerged as central symptoms within the CM-IA network. Additionally, "emotional abuse", "sexual abuse", and "complaints about online time" were identified as key bridge symptoms linking CM and IA. These symptoms demonstrated significant connectivity, underscoring their critical role in linking CM and IA. The findings highlight the complex relationship between CM and IA in adolescents with MDD. Specific symptoms, such as emotional abuse and online-related symptoms, play important roles in understanding and intervening in adolescent IA. Future interventions should target these core and bridge symptoms for more effective prevention and treatment.

Background: Studies have shown a strong association between childhood maltreatment (CM) and major depressive disorder (MDD). Dysfunctional attitudes (DAs) play a crucial role in the development of MDD. In this study, we aimed to investigate whether (1) DAs are associated with CM, (2) specific CM types predict specific types of DAs, and (3) higher childhood trauma counts (CTCs) predict more DAs.Methods: One hundred seventy-one MDD participants and 156 healthy controls (HCs) were enrolled for the study. CM was assessed retrospectively with the Childhood Trauma Questionnaire. DAs were evaluated using the Chinese version of the Dysfunctional Attitude Scale–Form A (C-DAS-A). A series of analyses, including multiple analyses of covariance and hierarchical regression analyses, were used in this study to examine the hypotheses.Results: The proportion of CM was 60.2% in the MDD group and 44.2% in the HC group. The 2 × 2 analysis of covariance results showed no interaction effect between CM and MDD on C-DAS-A total score. When the factor scores replaced the C-DAS-A total score, a similar trend was observed. Within the MDD group, emotional abuse (EA) predicted two forms of DAs: self-determination type and overall DAs; physical neglect (PN) was predictive of attraction and repulsion-type DAs. Higher childhood trauma counts significantly predicted more types of DAs in the MDD group.Conclusion: DAs are a trait feature of CM. EA and PN predict specific types of DAs in MDD patients. Higher CTCs predict more DAs in MDD patients.

Background: We investigated, for the first time, whether there are any sex differences in retrospective self-reported childhood maltreatment (CM) in Italian adult patients with major depressive disorder (MDD) or bipolar disorder (BD). Furthermore, the potential impacts of patients’ age on the CM self-report were investigated. Methods: This retrospective study used the data documented in the electronic medical records of patients who were hospitalized for a 4-week psychiatric rehabilitation program. CM was assessed using the 28-item Childhood Trauma Questionnaire (CTQ), which evaluates emotional, physical, and sexual abuse, as well as emotional and physical neglect. The linear and logistic regression models were used (α = 0.01). Results: Three hundred thirty-five patients with MDD (255 women and 80 men) and 168 with BD (97 women and 71 men) were included. In both samples, considerable CM rates were identified, but no statistically significant sex differences were detected in the variety of CTQ-based CM aspects. There was a significant association, with no sex differences, between increasing patients’ age and a decreasing burden of CM. Conclusion: Both women and men with MDD or BD experienced a similar and considerable CM burden. Our findings support routine CM assessment in psychiatric clinical practice.

Background: Childhood maltreatment (CM) is a significant risk factor for major depressive disorder (MDD), yet the underlying biological mechanisms remain unclear. This study aimed to investigate brain functional networks and peripheral transcriptomics in patients with MDD who have a history of CM. Methods: Functional imaging data were collected and network-based statistics were used to identify differences in functional networks among MDD patients with CM (MDD_CM, n = 78), MDD patients without CM (MDD_nCM, n = 61), and healthy controls (HC, n = 126). Additionally, blood transcriptional data were clustered into co-expression modules, and module differential connectivity analysis was utilized to assess variations in gene co-expression network modules among the groups. Results: The results revealed a significant difference in an inferior occipital gyrus-centered functional network among the three groups. Furthermore, eight gene co-expression modules differed among the groups and were enriched in multiple branches related to immune responses or metabolic processes. Notably, a module enriched in type I interferon-related signaling pathways demonstrated a significant correlation with the disrupted network in the MDD_nCM group. Moreover, multiple immune-related gene modules were found to be significantly correlated with sleep disturbances in MDD_CM patients. Conclusions: Dysregulation of an inferior occipital gyrus-centered functional network and immune-related transcriptomic alterations significantly associate with the pathophysiology of MDD_CM.

Childhood maltreatment (CM) is a major risk factor for developing the major depressive disorder (MDD), however, the neurobiological mechanism linking CM and MDD remains unclear. We recruited 34 healthy controls (HCs) and 44 MDD patients to complete the childhood maltreatment experience assessment with Childhood Trauma Questionnaire (CTQ) and resting-state fMRI scan. Multivariate linear regression analysis was employed to identify the main effects of CM and depressive symptoms total and subfactors scores on bilateral anterior and posterior insula functional connectivity (IFC) networks, respectively. Mediation analysis was performed to investigate whether IFC strength mediates the association between CM and depressive symptoms. MDD patients showed significantly decreased connectivity in the dorsal medial prefrontal cortex and increased connectivity in the medial frontal gyrus in the bipartite IFC networks, compared to HCs. The main effects of CM and depressive symptoms showed a large discrepancy on the anterior and posterior IFC networks, which primarily located in the frontal-limbic system. Further, conjunction analysis identified the overlapping regions linking CM and depressive symptoms were mainly implicated in self-regulation and cognitive processing circuits. More important, these IFC strengths could mediate the association between different types of CM, especially for childhood abuse and childhood neglect, and depressive symptoms in those overlapping regions. We demonstrated that early exposure to CM may increase the vulnerability to depression by influencing brain’s self-regulating and cognitive processing circuitry. These findings provide new insight into the understanding of pathological mechanism underlying CM-induced depressive symptoms.

BackgroundOvert aggression may be associated with childhood maltreatment (CM), insomnia, and alexithymia, but the underlying mechanisms of these associations have not been fully explored in adolescents with major depressive disorder (MDD). Therefore, the present study aimed to deeply analyze the relationships between overt aggression and CM, insomnia, and alexithymia in adolescents with MDD, to reveal the mediating mechanisms, and to provide a theoretical basis for clinical interventions.MethodsFrom December 2024 to December 2025, this study included 251 adolescents with MDD. The Modified Overt Aggression Scale (MOAS), the 17-item Hamilton Depression Rating Scale (HAMD-17), the Childhood Trauma Questionnaire (CTQ), the Insomnia Severity Index Scale (ISI), and the Toronto Alexithymia Scale (TAS-20) were used to assess the adolescents’ overt aggression, depression, CM, insomnia, and alexithymia. Additionally, we employed the PROCESS macro program to examine the mediating role of insomnia and alexithymia between CM and overt aggression.ResultsThe prevalence of overt aggression in adolescents with MDD was 66.1%. The regression analyses showed that age (Beta = -0.761, t = -2.967, P = 0.003), depression (Beta = 0.183, t = 2.676, P = 0.008), CM (Beta = 0.132, t = 4.048, P < 0.001), and alexithymia (Beta = 0.092, t = 1.990, P = 0.048) were independent correlates of overt aggression. When CTQ subscale scores involved in the regression model, age (Beta = -0.829, t = -3.257, P = 0.001), depression (Beta = 0.184, t = 2.618, P = 0.009), emotional abuse (Beta = 0.372, t = 4.081, P < 0.001), and insomnia (Beta = 0.170, t = 2.054, P = 0.041) were independent correlates. Moreover, alexithymia and insomnia played a chain mediating role between CM and overt aggression.ConclusionThe risk of overt aggression is significantly higher in depressed adolescents and is significantly associated with CM, insomnia, and alexithymia. Additionally, insomnia and alexithymia may play a mediating role between CM and overt aggression. Given these findings, comprehensive interventions for depressed adolescents with adverse childhood experiences, insomnia, and alexithymia, should be emphasized in clinical practice to effectively reduce their risk of overt aggression.

A Prospective Examination of Service Use by Abused and Neglected Children Followed Up Into Adulthood

Many studies have highlighted the detrimental effect of childhood maltreatment (CM) on depression severity and the course of illness in major depressive disorder (MDD). Yet our understanding of how CM influences the dynamic symptom change throughout a patient's trajectory remains limited. Hence, we investigated the impact of CM on depression severity in MDD with a focus on various treatment phases during inpatient treatment and after discharge (1 or 2 years later) and validated findings in a real-world setting. We used longitudinal data from a cohort study sample (n=567) and a clinical routine sample (n=438). CM was measured with the Childhood Trauma Questionnaire (CTQ), and depression severity was assessed using Beck's Depression Inventory (BDI). The long-term clinical trajectory was assessed using the Life Chart Interview. Our analyses revealed that CM significantly increased depression severity before, during, and after inpatient therapy in both samples. Although CM was associated with higher depression severity at the beginning of inpatient treatment and lower remission rates upon discharge, no discernible impact of CM was evident on the relative change in symptoms over time during inpatient treatment. CM consistently predicted higher relapse rates and lower rates of full remission after discharge during long-term follow-up in both samples. Our findings affirm the link between CM and the development of more severe and persistent clinical trajectories within real-world clinical settings. Furthermore, conventional psychiatric treatments may not lead to comparable outcomes for individuals with a history of CM, underscoring the necessity for tailored therapeutic interventions.

Childhood maltreatment correlates with higher concentration of transforming growth factor beta (TGF-β) in adult patients with major depressive disorder