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Updated: Mar 14, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Childhood trauma and HPA axis functionality in offspring of bipolar parents
Merel M Schreuder1, Christiaan H Vinkers1, Esther Mesman1
1Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
Childhood trauma impacts daytime cortisol levels in individuals with a familial risk for bipolar disorder. These trauma-related changes in hypothalamic-pituitary-adrenal (HPA) axis activity are specific to bipolar offspring.
Area of Science:
- Neuroscience
- Psychiatry
- Endocrinology
Background:
- Children of parents with bipolar disorder (bipolar offspring) face heightened risk for mood disorders.
- Genetic factors and environmental stress, such as childhood trauma, contribute to this vulnerability.
- Childhood trauma is linked to persistent hypothalamic-pituitary-adrenal (HPA) axis dysfunction.
Purpose of the Study:
- To investigate the impact of childhood trauma on HPA axis activity in bipolar offspring.
- To compare daytime and evening cortisol levels and dexamethasone suppression between bipolar offspring and healthy controls.
Main Methods:
- Assessed daytime and evening cortisol levels and dexamethasone suppression.
- Examined 70 bipolar offspring and 44 healthy controls.
- Analyzed the interaction between childhood trauma and bipolar offspring status on HPA axis measures.
Main Results:
- No significant differences in overall cortisol levels or dexamethasone suppression were found between groups.
- Childhood trauma significantly affected daytime cortisol levels in bipolar offspring compared to controls (p=0.0414).
- Trauma-related changes in daytime HPA axis activity appear specific to bipolar offspring.
Conclusions:
- Childhood trauma specifically alters daytime HPA axis activity in bipolar offspring.
- These findings highlight a potential biomarker for mood disorder risk in families with bipolar disorder.
- Trauma-related HPA axis alterations may represent a specific trait in individuals at familial risk for mood disorders.
Abstract:
Children of a parent with bipolar disorder (bipolar offspring) have an increased risk for mood disorders. While genetic factors play a significant role in this population, susceptibility to environmental stress may also significantly contribute to this vulnerability for mood disorders. Childhood trauma has consistently been found to increase the risk for mood disorders, with persisting consequences for hypothalamic-pituitary-adrenal (HPA) axis functionality. However, it is currently unknown whether childhood trauma specifically affects HPA axis activity in individuals with a familial risk for bipolar disorder. Therefore, we investigated the effects of childhood trauma on daytime and evening cortisol levels and dexamethasone suppression in bipolar offspring (N=70) and healthy controls (N=44). In our study we found no significant differences in daytime and evening cortisol levels as well as dexamethasone suppression between bipolar offspring and healthy controls (all p-values>0.43). In contrast, childhood trauma differentially affected daytime cortisol levels in the bipolar offspring compared to healthy controls (childhood trauma X bipolar offspring interaction, β=-7.310, p=0.0414) with an effect of childhood trauma on daytime cortisol in bipolar offspring at trend level (p=0.058). In the bipolar offspring group, lifetime or current psychiatric diagnoses, and stressful life events separately did not affect cortisol levels or dexamethasone suppression (all p-values>p=0.50). These findings were independent of current or lifetime psychiatric diagnosis. In conclusion, trauma-related changes in daytime HPA axis activity appear to be a specific trait in bipolar offspring who have increased risk for mood disorders compared to healthy individuals.
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