Parental cancer and children’s well-being : understanding the potential role of psychological stress

Early life stress has a major influence on one’s health through the life course. During childhood, early experience may not only affect the normal brain development, but also influence the susceptibility to mental and physical disorders. A cancer diagnosis in a parent may cause substantial distress in the children, who may have to confront and adapt to short- and long-term changes in their lives and subsequently experience a higher risk of physical and psychosocial problems. Therefore, the first aim of this thesis was to examine whether parental cancer is associated with physical and mental health problems in the affected children using data from the Swedish national registers. Further, to explore the potential mechanism determining the impact of stress on children’ health, we focused on the brain development in childhood and investigated the association between stress biomarkers and brain morphology, using data from a Dutch population-based cohort.

In Study I, we assessed the association between parental cancer and risk of injury in a large representative sample of Swedish children. We found that parental cancer was associated with a higher risk of hospital contacts for injury, particularly during the first year after the cancer diagnosis and when the parent experienced a psychiatric illness after the cancer diagnosis. The risk increment reduced during the second and third years and became null afterwards.

Given the observed higher risk of adverse physical health in terms of injury, we further investigated the influence of parental cancer on adverse mental health in terms of psychiatric disorders among children. In Study II, we constructed a matched cohort, and separately examined the associations between parental cancer diagnosed during pregnancy or after birth and clinical diagnoses of psychiatric disorders or use of prescribed psychiatric medications. Paternal but not maternal cancer during pregnancy appeared to be associated with a higher risk of psychiatric disorders, primary among girls. Parental cancer after birth conferred a higher risk of clinical diagnoses of psychiatric disorders, particularly stress reaction and adjustment disorders. The affected children also experienced a higher risk of use of prescribed psychiatric medications, particularly anxiolytics. The latter associations were most pronounced for parental cancer with poor expected survival and for parental death after cancer diagnosis.

In Study III, we focused on other domains of mental and physical health affected by parental cancer. We examined the associations of parental cancer with intellectual performance, stress resilience, and physical fitness among boys that underwent the compulsory military conscription examination during early adulthood. We observed positive associations of parental cancer with low stress resilience and low physical fitness, with stronger associations noted for parental cancer with poor expected survival and for a loss of parent through death after cancer diagnosis. No overall association was observed between parental cancer and intellectual performance, but the parental cancer with poor expected survival or resulting in a death of the parent was associated with a higher risk of low intellectual performance.

The hypothalamic-pituitary-adrenal (HPA) axis is one of the most extensively studied stress systems. Detection of glucocorticoids in hair has emerged as an approach to measuring HPA activity retrospectively. In Study IV, we assessed the associations of hair cortisol and cortisone concentrations with brain morphology in a population-based sample of young children in Rotterdam, the Netherlands. The regions of interest analyses showed that hair cortisol and cortisone concentrations were positively associated with cortical surface area in the parietal lobe. However, an inverse association was found between hair cortisol or cortisone concentration and hippocampal volume in children with behavioral problems. The vertex-wise analyses with correction for multiple testing did, however, not show any association of hair cortisol or cortisone concentration with cortical thickness, cortical surface area or gyrification.

In conclusion, parental cancer, a potent early life stressful event, is associated with a higher risk of physical and mental health outcomes, including injuries, psychiatric disorders, low intellectual performance, low stress resilience, and low physical fitness. Although we did not find clear associations of hair cortisol and cortisone concentrations with brain morphology in typically developing children, children that are evidently exposed to psychological stress should be provided adequate support and care to prevent from stress-related health outcomes.

List of scientific papers

I. Chen R, Regodón Wallin A, Sjölander A, Valdimarsdóttir U, Ye W, Tiemeier H, Fall K, Almqvist C, Czene K, Fang F. Childhood injury after a parental cancer diagnosis. Elife. 2015 Oct 31;4. pii: e08500.
https://doi.org/10.7554/eLife.08500

II. Chen R, Regodón Wallin A, Norén Selinus E, Sjölander A, Fall K, Valdimarsdóttir U, Czene K, Fang F. Psychiatric disorders among children with parental cancer: a Swedish register-based matched cohort study. [Submitted]

III. Chen R, Fall K, Czene K, Kennedy B, Valdimarsdóttir U, Fang F. Is parental cancer associated with intellectual, psychological and physical performance in early adulthood? [Submitted]

IV. Chen R, Muetzel RL, El Marroun H, Noppe G, van Rossum EF, Jaddoe VW, Verhulst FC, White T, Fang F, Tiemeier H. No association between hair cortisol or cortisone and brain morphology in children. Psychoneuroendocrinology. 2016 Aug 24;74:101-110.
https://doi.org/10.1016/j.psyneuen.2016.08.023