Inflammatory measures in depressed patients with and without a history of adverse childhood experiences

Background: Major depressive disorder (MDD) is a complex psychiatric condition with different subtypes and etiologies. Exposure to adverse childhood experiences (ACE) is an important risk factor for the development of MDD later in life. Evidence suggests that pro-inflammatory processes may convey this risk as both MDD and ACE have been related to increased levels of inflammation. In the present study, we aimed to disentangle the effects of MDD and ACE on inflammation levels. Methods: Markers of inflammation (plasma interleukin(IL)-6 and high sensitive C-reactive protein (hsCRP) concentrations, white blood cell (WBC) count and a composite inflammation score (CIS) combining all three) were assessed in 23 MDD patients with ACE, 23 MDD patients without ACE, 21 healthy participants with ACE, and 21 healthy participants without ACE (mean age: 35 +/- 11 (SD) years). None of the patients and participants was taking psychotropic medication. ACE was assessed with the Early Trauma Inventory (ETI) and was defined as moderate to severe exposure to sexual or physical abuse. Results: Group differences in the different inflammatory measures were observed. MDD patients with ACE showed significantly higher IL-6 concentrations (p = 0.018), higher WBC counts (p = 0.003) and increased general inflammation levels as indicated by the CIS (p = 0.003) compared to healthy controls. In contrast, MDD patients without ACE displayed similar inflammation levels to the control group (p = 0.93). Conclusion: We observed elevated inflammation in MDD patients with a history of ACE, which could indicate a subtype of "inflammatory depression". Accordingly, MDD patients with ACE might potentially benefit from anti-inflammatory therapies

Inflammatory Measures in Depressed Patients With and Without a History of Adverse Childhood Experiences

Background: Major depressive disorder (MDD) is a complex psychiatric condition with different subtypes and etiologies. Exposure to adverse childhood experiences (ACE) is an important risk factor for the development of MDD later in life. Evidence suggests that pro-inflammatory processes may convey this risk as both MDD and ACE have been related to increased levels of inflammation. In the present study, we aimed to disentangle the effects of MDD and ACE on inflammation levels.Methods: Markers of inflammation (plasma interleukin(IL)-6 and high sensitive C-reactive protein (hsCRP) concentrations, white blood cell (WBC) count and a composite inflammation score (CIS) combining all three) were assessed in 23 MDD patients with ACE, 23 MDD patients without ACE, 21 healthy participants with ACE, and 21 healthy participants without ACE (mean age: 35 ± 11 (SD) years). None of the patients and participants was taking psychotropic medication. ACE was assessed with the Early Trauma Inventory (ETI) and was defined as moderate to severe exposure to sexual or physical abuse.Results: Group differences in the different inflammatory measures were observed. MDD patients with ACE showed significantly higher IL-6 concentrations (p = 0.018), higher WBC counts (p = 0.003) and increased general inflammation levels as indicated by the CIS (p = 0.003) compared to healthy controls. In contrast, MDD patients without ACE displayed similar inflammation levels to the control group (p = 0.93).Conclusion: We observed elevated inflammation in MDD patients with a history of ACE, which could indicate a subtype of “inflammatory depression”. Accordingly, MDD patients with ACE might potentially benefit from anti-inflammatory therapies

Doublecortin (DCX) and doublecortin-like (DCL) are differentially expressed in the early but not late stages of murine neocortical development

During corticogenesis, radial glia-derived neural progenitors divide and migrate along radial fibers to their designated positions within the cortical plate. The microtubule-associated proteins doublecortin (DCX) and doublecortin-like (DCL) are critically involved in neuronal migration and division, and may function in a partially redundant pathway. Since little is known about the important early stages of corticogenesis, when neurogenesis is extensive, we addressed a possible differential role by examining spatiotemporal expression patterns of DCX, DCL, and the radial glia marker vimentin during murine development. We found expression patterns of DCL and DCX to differ remarkably prior to embryonic day (E)13. DCL was already expressed at E9 and largely overlapped with vimentin, whereas DCX expression started modestly from E10/E11 onward. DCL was mainly found in the ventricular zone, often in mitotic cells and in pial-oriented radial fibers. In contrast, DCX was expressed in tangential fibers in the outer cortical regions. After E13, DCX and DCL expression largely overlapped but DCL expression had disappeared from the ventricular zone. Also, DCL levels were attenuated, whereas DCX remained high beyond E17. In conclusion, DCX and DCL are differentially expressed, particularly during early corticogenesis, consistent with their different functional roles. Given its involvement in mitosis, DCL appears to have a unique role in the early neuroepithelium that is different from later developmental stages when DCX is coexpressed

Immediate and longitudinal effects of maltreatment on systemic inflammation in young children

Exposure to child maltreatment increases the risk for psychiatric and physical diseases. Inflammation has been proposed as a mechanism through which early adverse experiences become biologically embedded. However, most studies providing evidence for the link between early adverse exposures and inflammation have been retrospective or cross-sectional in design, or did not assess inflammation immediately after maltreatment in young children. In the present study we investigated the association between childhood maltreatment and salivary C-reactive protein (CRP) concentrations in a population of N = 173 children, 3-5 years of age, who were recruited in the immediate aftermath of maltreatment and followed-up longitudinally every 6 months over a period of 2 years. We found that the association between maltreatment and CRP concentrations was significantly moderated by child sex, such that in girls, CRP concentrations were higher in the maltreated compared to the control group, and this difference was stable across the 2-year follow-up-period, while in boys, there was no association between maltreatment and CRP. Our findings suggest that the effect of maltreatment on inflammation may already emerge right after exposure at a very young age in girls and manifest over time. Our study provides important evidence for the development of personalized, early interventions strategies targeting the early-life period