The psychopathological potential of early life stress

In the second decade of the twenty-first century, there has been an eruption of studies on the pathogenic role of stress in early life, named also ‘early life adversity’ or ‘childhood trauma’, in psychiatric disorders. Many such papers have been published in our journal in recent years and this topic was also reflected in most of the articles of the seventh issue 2020.

In their review of the epigenetic alterations associated with childhood trauma in relation to adult mental health outcomes, Nöthling et al. (2020) point to the role of the epigenetic processes among which methylation is the most important. The genes mainly influenced by the inappropriate methylation include the glucocorticoid receptor NR3C1 gene, serotonin transporter SLC6A4 gene, brain-derived neurotrophic factor BDNF gene, oxytocin receptor OXTR gene, and FK 506 binding protein FKBP5 gene. All these genes were found significant in the mechanisms of childhood trauma (Jaworska-Andryszewska and Rybakowski 2019) and will be repeatedly mentioned in the further parts of the editorial. The authors argue that epigenetic modification is most important for translating the early life stress into psychiatric disorders of adult life. Such importance was confirmed, among others, by Russian researchers in relation to chronic physical aggression (Chistiakov and Chekhonin 2019).

Womersley et al. (2020) studied a mediation between childhood emotional neglect and changes in brain structures due to the oxytocin receptor gene (OXTR) variants. They showed that the rs2254298 A risk allele of the OXTR gene was independently associated with reduced left hippocampal volume and reduced bilateral amygdala volumes. Earlier, Schiele et al. (2018) found that this polymorphism of the OXTR gene was associated with an interaction between behavioural inhibition and separation anxiety in vulnerability for complicated grief. Furthermore, Monteleone et al. (2019) confirmed the effect of childhood trauma on brain structures.

The Irish investigators (Jairaj et al. 2020) assessed the hypothalamic-pituitary-adrenal (HPA) axis function in the perinatal period in relation to major depressive disorder and early life adversity (ELA). They found that a history of ELA regardless of comorbid depression was associated with higher evening cortisol levels during pregnancy. They postulated that this phenomenon may be connected with a higher risk of both antenatal and postpartum depression.

The biomarkers in pregnancy were also a topic of the paper by Levitan et al. (2020). They investigated plasma tryptophan and kynurenine concentrations in pregnant women depending on a history of full or subsyndromal seasonal affective disorder. The paper marks more than half a century of the kynurenine hypothesis of depression (Lapin and Oxenkrug 1969). The authors found significant differences in both these substances related to maternal seasonality and season of conception. These findings may have implications for risk of depression in pregnancy and also for foetal brain development.

Labad et al. (2020) studied the HPA function and cannabis use in recent-onset psychosis in relation to childhood trauma and stressful life events. They found that cannabis use was associated with a more flattened diurnal cortisol slope independent of recent-onset psychosis diagnosis. However, no relationship was found with childhood trauma and stressful life events.

Kleine Deters et al. (2020) in an international study assessed executive functioning and emotion recognition in young patients, aged 8–18 years with the oppositional defiant disorder (ODD) and/or conduct disorder (CD) compared with healthy subjects of this age. They found that visual working memory and inhibitory control were impaired in both conditions. However, these deficits were not explained by comorbid attention-deficit/hyperactivity disorder (ADHD) or internalising symptoms. These findings challenge the view that neuropsychological impairments in youth with ODD/CD are driven by comorbid ADHD and suggest distinct neurocognitive mechanisms.

In the era of Covid-19 pandemics, the paper on this topic should not be missing. This claim was fulfilled by the report of the German authors (Schmidt and Rein 2020) on the novel treatment targets for Covid-19. According to them, such a target could be a stress protein, FK 506 binding protein, associated with various mental disorders such as major depression and post-traumatic stress disorder (PTSD). They suggest that this protein could modify the neuroinvasive potential of the SARS-CoV-2 virus. The reader of this editorial may recall that the gene for this protein (FKBP5) was mentioned at the beginning of the article as instrumental for the effects of early life stress. A recent example of the role of the FKBP5 gene in the sequels of childhood abuse is the results of the paper of Tamman et al. (2019). The authors found that the polymorphism of this gene may predict the risk for PTSD exerted by the childhood abuse and that attachment style may moderate this effect.