Adult retrospective report of child abuse and prospective indicators of childhood harm: a population birth cohort study

Background We aim to determine whether adult retrospective report of child abuse is associated with greater risk of prospectively assessed harmful environments in childhood. We assessed possible recall basis by adult depression status. Methods At 45 years, participants of the 1958 British birth cohort (N = 9308) reported a range of abuse types (by 16 years). Prospective data, ages 7–16 years, were obtained for impoverished upbringing, hazardous conditions, anti-social behaviours and 16 years poor parent-child relationships. We estimated associations between retrospective report of child abuse and prospectively measured harm using (i) odds ratios (ORs, 95% confidence intervals) and (ii) positive predictive values (PPVs). PPVs were calculated stratified by adult depression status. Results Prevalence of retrospectively reported abuse ranged from 10.7% (psychological) to 1.60% (sexual) and 14.8% reported ≥ 1 type; prospectively recorded harm ranged from 10% (hazardous conditions/poor parent-child relationships) to 20% (anti-social behaviours). Adults retrospectively reporting abuse were more likely to have had harmful childhood environments: 52.4% had ≥ 1 indicator of harm (vs. 35.6% among others); ORsex-adjusted for poor relationships with parents was 2.98 (2.50, 3.54). For retrospectively reported (vs. none) abuse, there was a trend of increasing relative risk ratio with number of harms, from 1.75 (1.50, 2.03) for 1 to 4.68 (3.39, 6.45) for 3/4 childhood harms. The PPV of ≥ 1 prospectively recorded harm did not differ between depressed (0.58 (0.52, 0.64)) and non-depressed (0.58 (0.55, 0.61)) groups. Conclusions In a population cohort, adult retrospective report of child abuse was associated with several harms, prospectively measured from childhood to adolescence, providing support for the validity of retrospective report-based research. Findings suggest retrospectively reported child abuse is not biased by depression in adulthood.

Early Life Irradiation-Induced Hypoplasia and Impairment of Neurogenesis in the Dentate Gyrus and Adult Depression Are Mediated by MicroRNA- 34a-5p/T-Cell Intracytoplasmic Antigen-1 Pathway

Early life radiation exposure causes abnormal brain development, leading to adult depression. However, few studies have been conducted to explore pre- or post-natal irradiation-induced depression-related neuropathological changes. Relevant molecular mechanisms are also poorly understood. We induced adult depression by irradiation of mice at postnatal day 3 (P3) to reveal hippocampal neuropathological changes and investigate their molecular mechanism, focusing on MicroRNA (miR) and its target mRNA and protein. P3 mice were irradiated by γ-rays with 5Gy, and euthanized at 1, 7 and 120 days after irradiation. A behavioral test was conducted before the animals were euthanized at 120 days after irradiation. The animal brains were used for different studies including immunohistochemistry, CAP-miRSeq, Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) and western blotting. The interaction of miR-34a-5p and its target T-cell intracytoplasmic antigen-1 (Tia1) was confirmed by luciferase reporter assay. Overexpression of Tia1 in a neural stem cell (NSC) model was used to further validate findings from the mouse model. Irradiation with 5 Gy at P3 induced depression in adult mice. Animal hippocampal pathological changes included hypoplasia of the infrapyramidal blade of the stratum granulosum, aberrant and impaired cell division, and neurogenesis in the dentate gyrus. At the molecular level, upregulation of miR-34a-5p and downregulation of Tia1 mRNA were observed in both animal and neural stem cell models. The luciferase reporter assay and gene transfection studies further confirmed a direct interaction between miR-43a-5p and Tia1. Our results indicate that the early life γ-radiation-activated miR-43a-5p/Tia1 pathway is involved in the pathogenesis of adult depression. This novel finding may provide a new therapeutic target by inhibiting the miR-43a-5p/Tia1 pathway to prevent radiation-induced pathogenesis of depression.

The long arm of childhood: The prolonged influence of adverse childhood experiences on depression during middle and old age in China

Utilizing data from the nationally representative China Health and Retirement Longitudinal Study, this study analyzed the effect of intensity and duration of adverse childhood experiences on depression in middle aged and older aged adults in China. The mediating effect of cumulative health risk and personal factors were validated through the Karlson–Holm–Breen method. The results showed a significant dose-response relationship between adverse childhood experiences and adult depression. The elevated health risks of chronic diseases, disabilities, and physical pain, as well as the disadvantages in education, employment, and economic status caused by the adverse childhood experiences indirectly worsen adult depression.

Influence of Childhood Family Routines on Adult Depression: A Cross Sectional Study

In order to explore the influence of childhood family routines on adult depression and the mediating role of tolerance of uncertainty and rumination, the current study tested 818 participants by adopting four questionnaires. The results of structural equation modeling revealed that (1) family routines had a negative effect on depression among Chinese college students; (2) family routines were found to have a positive effect on tolerance of uncertainty, and tolerance of uncertainty was a bridge linking family routines and depression; (3) family routines had a significant effect on depression through rumination; (4) the relationship between family routines and depression was partially mediated by the chain of tolerance of uncertainty and rumination. The result reveals not only the fact that childhood family routines have significant influence on college students' depression but also the mechanism of childhood family routines that affect college students' depression. The limitations and implications of our study were also discussed.

Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice

The number of young adult patients with major depression, one of the most common mental disorders, is gradually increasing in modern society. Stressful experiences in early life are considered one of the risk factors for chronic depressive symptoms, along with an abnormal inflammatory response in later life. Although increased inflammatory activity has been identified in patients with depression, the cause of long-lasting depressive states is still unclear. To identify the effects of cumulative mild stress in brain development periods, we generated a young adult depression mouse model exposed to cumulative mild stress (CPMS; cumulative mild prenatal stress, mild maternal separation, and mild social defeat) to mimic early life adversities. CPMS mice exhibited more long-lasting anxiety and depression-like behaviors than groups exposed to single or double combinations of mild stress in young adult age. Using the molecular works, we found that inflammatory cytokines, especially interleukin (IL)-17, upregulated microglial activation in the hippocampus, amygdala, and prefrontal cortex of CPMS mice. In the brains of CPMS mice, we also identified changes in the T helper (Th)-17 cell population as well as differentiation. Finally, anti-IL-17 treatment rescued anxiety and depression-like behavior in CPMS mice. In conclusion, we found that cumulative mild stress promoted long-lasting depressive symptoms in CPMS mice through the upregulation of IL-17. We suggest that the CPMS model may be useful to study young adult depression and expect that IL-17 may be an important therapeutic target for depression in young adults.