Research indicates that early-life stress may aggravate depression in adulthood

Study conducted at the University of São Paulo, in partnership with a researcher from King’s College London, notes that mistreatment during childhood and adolescence leads to changes in the psychoneuroendocrine system.

By Samuel Antenor

Agência FAPESP – A research study performed at the Ribeirão Preto School of Medicine of the University of São Paulo (FMRP-USP) has determined that so-called early-life stress – a term that includes both trauma and physical mistreatment as well as sexual and emotional abuse suffered by children and teens – may worsen depression in adult life.

Led by Mario Juruena, a professor in the Department of Neurosciences and Behavioral Sciences at FMRP, the study both detected permanent records in the brains of those who experienced this type of stress and established a way to identify cause-and-effect relationships in different types of depression.

In partnership with Professor Anthony Cleare of King’s College London, the British institution that has a cooperation agreement with FAPESP, Juruena identified alterations in the hypothalamus-pituitary-adrenal (HPA) axis – the part of the neuroendocrine system that perceives situations that cause stress – as a result of early-life stress in patients with depressive psychopathologies in adulthood.

Developed in collaboration with the Department of Psychological Medicine in the Section of Neurobiology of Mood Disorders at the Institute of Psychiatry of King’s College, the study analyzed the association between physical, sexual and emotional abuse and neglect during childhood and both specific alterations in the HPA axis and the function of the receptors of hormones responsible for cellular metabolism. The goal was to analyze the effect of imbalances caused by early-life stress on two prevalent subtypes of depression: atypical and melancholic.

“We wanted to evaluate atypical and melancholic depression in adults with hard-to-treat forms of the disease, a situation that tends to occur more frequently when there is a history of early-life stress,” Juruena told Agência FAPESP. According to him, previous studies and clinical care experiences indicate that in general, half of all cases of depression do not respond to treatment.

The patients studied were divided into three separate groups, all of which were assessed for their level of secretion of the hormone cortisol and its correlation to receptors.

The first group consisted of people with a history of early-life stress and depression. The second group included people suffering from depression but with no history of early-life stress. The third group (control) involved healthy individuals with no history of abuse or symptoms of depression.

All patients were given the Childhood Trauma Questionnaire (CTQ), a type of questionnaire about childhood trauma that includes questions about sexual, physical and emotional abuse and physical and emotional neglect.

An assessment was also made regarding the function of cortisol receptors in each of the subjects, correlating the psychometric results for the severity of the depression and stress with the neurobiological results for the HPA axis and receptors.

The research subjects were also administered corticoid substances such as fludrocortisone, prednisolone, spironolactone and dexamethasone. These substances interact differently and selectively with the cortisol receptors and indicate the receptor in which the patient presents dysfunctions of the HPA axis, based on the secretion of cortisol analyzed in saliva samples.

In total, 80% of the patients in the first group received a diagnosis of atypical depression. Among the symptoms of this type of depression are hyperphagia (the tendency to overeat, especially sweets and carbohydrates) and hypersomnia (the propensity to sleep a lot) which are the results of a very low release of cortisol by the HPA axis.

In contrast, most of the patients in the second group were diagnosed with melancholic depression. In this case, the imbalance in the HPA axis causes the release of high levels of cortisol, leading to insomnia and loss of appetite.

Genetics and epigenetics

According to the FMRP professor, the research indicated that early-life stress influences individuals considered to be susceptible to presenting with one of the subtypes of depression in adulthood.

Even though they experience traumatic events during childhood and adolescence, certain people do not end up developing depressive conditions because they do not present with genetic predisposition to depression due to “having some sort of resilience,” Juruena said.

“Depression demonstrates an interaction between an individual’s vulnerability and the adverse environment in which he lived or lives. If an individual who is genetically predisposed to depression is abused, the risks of developing the disease increase substantially. This occurs due to epigenetic factors, or, in other words, the influence that external factors [environmental, socioeconomic] have on an individual’s physical and psychic make-up,” he said.

According to Juruena, although protein synthesis is related to the genetic heritage of each person, children who experience early-life stress have modified protein release characteristics. In the presence of depressive conditions, environmental factors exert double the influence as genetic factors do.

“When a child experiences early-life stress, that information impacts the HPA axis, which leaves scars. In adult life, this causes the depression to be more severe. A depressed person begins to have his physical-emotional condition determined by this alteration, presenting oscillations up or down in the levels of hormones such as cortisol, depending on the subtype of depression,” Juruena said.

Work conducted by the researcher indicates that nearly 70% of patients with depression have a history of abuse. In addition to being more resistant to treatments, they also present higher rates of relapse and comorbidity.

“The discussion surrounding laws that prevent child abuse refers to physical abuse, but little attention is given to emotional abuse, which involves verbal insults, humiliation and aggression against children. Aggression with words also leaves scars, however, and promotes the development of pathologies in adult life, as we have seen in the research,” Juruena said.

“Emotional abuse and neglect during a child’s development are factors that cause the most impact on the severity of the depression,” he said.

Joint study

To Juruena, who earned his doctorate and did post-doctoral studies at the Institute of Psychiatry at King’s College, the knowledge developed about depression in the Section of Mood Disorders at the institution has helped to enhance his research at FMRP.

“Depression is a disease that is highly resistant to treatment, with factors that can influence the severity of the symptoms and generate chronicity. This study has allowed us to obtain data that help to corroborate such evidence, as already pointed out in previous studies carried out in collaboration with the team of Professor Anthony Cleare,” he said.

According to Juruena, other studies in Brazil have also addressed the topic recently, including work performed by the FMRP-USP Program of Assistance, Education and Research on Stress, Trauma and Mood Disorders (EsTraDA), of which he is also a part. However, the researcher notes that new studies are needed to clarify the mechanisms involved in connecting early-life stress with depression in adult life.

Findings from the study have been published in several journals:

• Journal of Affective Disorders
• Journal of Psychopharmacology
• The Journal of Nervous and Mental Disease
• Frontiers of Psychiatry
• Epilepsy & Behavior
• Acta Neuropsychiatrica