įurther, early life factors may modify the role of genetic polymorphism by providing the necessary substrates for the development of human disease or influencing the effect of a specific gene. Early life stress affects hippocampal neurogenesis, increases depressive-like behavior, and causes mild metabolic imbalance in early adulthood (2 months). Altered hypothalamic-pituitary-adrenal (HPA) axis regulation and secondary regional brain structure changes in children exposed to emotional abuse, sexual abuse, and aggressive families. For example, childhood trauma exposure is associated with altered brain structure and function. Relative to adulthood, neurodevelopment during childhood and adolescence is more plastic and susceptible to programming influences from stressful environmental and social contexts. The early life factors of the newborn are crucial in the adaptation to (potentially life-long) environmental exposures. Therefore, the age at onset of the depression is important for the development of depression. In a recent large cohort study of adults aged 18–88 years, people aged 70 and above experienced greater symptom severity compared with younger adults. With increasing age, the course of depression became worsens.
It has long been suggested that early onset MDD is associated with increased risk of the disorder in first degree relatives, while late onset MDD was associated with increased familial risk of vascular disease. Early-onset depression and late-onset depression may have different pathogenesis.
Children having parents with early onset major depressive disorder (MDD) (30) MDD is estimated to be much lower ( h 2 = 0.10). The age at onset of depression is the main reason for the clinical heterogeneity of depression. Various factors including different age at onset of the depressive episode, varying symptom profiles, different levels of symptom severity, and duration may contribute to clinical heterogeneity. ĭepression is a highly heterogeneous syndrome. According to the report of WHO, the global population suffering from depression was estimated to be 322 million, accounting for 4.4% of the global population that resulting in a surge in suicide rates as well as a huge social and economic burden. Over the past several decades, the amount of people with depression have increased leading to a growing concern in mental health research around the world. Our results indicate emotional care in childhood may affect the age at onset of depression, especially in males, and GSAP plays an important role in their interaction.ĭepression is a widespread chronic medical illness often presenting with physical symptoms. GWEIS identified a novel candidate loci interacting with felt loved as a child at GSAP (rs2068031, P = 4.24 × 10 –8) and detected several genes with suggestive significance association, such as CMYA5 (rs7343, P = 2.03 × 10 –6) and KIRRE元 (rs535603, P = 4.84 × 10 –6) in males. In regression analyses, we observed significant interacting effects of felt loved as a child and depression PRS on the age at onset of depression in total sample ( β = 0.708, P = 5.03 × 10 −3) and males ( β = 1.421, P = 7.64 × 10 −4). Genome-wide environment interaction studies (GWEIS) were then performed to identify the genes interacting with early life factors for the age at onset of the depression.
Regression analyses were conducted to assess the interacting effects of depression PRS and 5 early life factors, including felt hated by family member ( N = 40,112), physically abused by family ( N = 40,464), felt loved ( N = 35633), and sexually molested ( N = 41,595) in childhood and maternal smoking during pregnancy ( N = 38,309), on the age at onset of the depression. Based on previous genome-wide association study (GWAS) data, we first calculated polygenic risk score (PRS) for depression.
However, they only focused on the influence of environmental or genetic factors, without considering the interactions between them. Multiple previous studies explored the associations between early life factors and the age at onset of the depression.