Summary: Depressed adolescents with a history of physical or sexual abuse had metabolites related to oxidative stress and transsulfuration. Both transsulfuration and oxidative stress regulate each other’s functions and are associated with inflammation.
Source: University of Eastern Finland
A pilot study conducted at the University of Eastern Finland found metabolites related to oxidative stress and the transsulfuration pathway of one-carbon metabolism to be associated with a history of sexual or physical abuse in depressed adolescent outpatients.
Oxidative stress and transsulfuration are closely connected and regulate each other’s functions, and they play a role in inflammation, which is also recognized as a possible mechanism of trauma.
The results were published in a peer-reviewed scientific journal, the European Journal of Psychotraumatology, in a special issue entitled “Biological mechanisms underlying adverse mental health outcomes after trauma.”
“Although the results are clearly preliminary and require further confirmation, the extent of similar findings in the literature related to the biological effects of trauma is convincing. Oxidative stress and the inflammatory system have often been associated with post-traumatic stress.
“Oxidative stress refers to an excess of unstable oxygen-containing molecules, which damage cells and have numerous consequences, whereas the end product of transsulfuration is an antioxidant compensating for this damage,” says Doctoral Researcher Karoliina Kurkinen from the University of Eastern Finland.
The study included 76 depressed adolescent outpatients, whose blood samples were analysed with mass spectrometry to determine the concentrations of specific metabolites.
The study included 76 depressed adolescent outpatients, whose blood samples were analysed with mass spectrometry to determine the concentrations of specific metabolites. Image is in the public domain
In addition to metabolites taking part in oxidative stress and transsulfuration, metabolites related to the methionine cycle of one-carbon metabolism, mitochondrial dysfunction and inflammation were also found to be associated with a history of abuse in these patients. These associations became smaller after taking into account depression and lifestyle-related background variables.
This exploratory pilot study should be replicated with a larger data set comprising post-traumatic stress disorder patients and healthy controls. In addition, future research could examine the levels of hypothalamic–pituitary–adrenal axis hormones and interleukins to take stress and inflammation better into consideration.
“Depression is a very common symptom in traumatized patients, but so are fight and flight-related symptoms, which relate to stress and activation of the sympathetic nervous system.
“It would be interesting to further investigate the biological mechanisms behind these two different symptom clusters, how they overlap and affect each other, and which pathways would be most helpful to intervene in for a traumatized patient,” Kurkinen says.
The associations between metabolic profiles and sexual and physical abuse in depressed adolescent psychiatric outpatients: An exploratory pilot study
Background: Sexual and physical abuse have been associated with long-term systemic alterations such as low-grade inflammation and changes in brain morphology that may be reflected in the metabolome. However, data on the metabolic consequences of sexual and physical abuse remain scarce.
Objective: This pilot study sought to investigate changes in the metabolite profile related to sexual and physical abuse in depressed adolescent psychiatric outpatients.
Method: The study included 76 patients aged 14–18 years, whose serum samples were analysed with a targeted metabolite profiling methodology. We estimated the associations between metabolite concentrations and the Trauma and Distress Scale (TADS) Sexual and Physical Abuse factor scores using three linear regression models (one unadjusted and two adjusted) per metabolite and trauma type pair. Additional variables in the two adjusted models were 1) the lifestyle indicators body mass index, tobacco use, and alcohol use, and 2) depression scores and the chronicity of depression.
Results: TADS Sexual Abuse scores associated positively with homogentisic acid, as well as cystathionine, and negatively with choline in linear regression analysis, whereas TADS Physical Abuse scores associated negatively with AMP, choline, γ-glutamyl cysteine and succinate, and positively with D-glucuronic acid.
Conclusions: This pilot study did not include a healthy control group for comparison and the cohort was relatively small. Nevertheless, we observed alterations in metabolites related to one-carbon metabolism, mitochondrial dysfunction, oxidative stress, and inflammation in depressed patients with a history of sexual or physical abuse.