Infant Temperament Predicts Cancer Onset in Female Rats

Rats’ willingness to explore a novel environment was tested in a modification of the “novel room situation” used to assess temperament in young children. With rat-sized novel objects, opaque walls and a reassuring cover– the test is designed to minimize rat anxiety and allow the animals to explore a full range of responses to benign novelty. To measure exploration, the arena was divided into a 3×3 grid and researchers counted the number of times a rat moved from one adjacent square to another.

Based on their behavior, the rats were categorized as of “neophobic” ,”neophilic”, or “intermediate” temperaments. Neophobic infant rats (20 days old) explored the environment 6 times less than their neophilic sisters, visiting 8 squares compared with 47 in the neophilic animals. When tested again in adulthood, this temperament difference persisted, although it became less pronounced.

Females that had been neophobic as infants developed mammary tumors earlier than neophilic females. 80% of the neophobic rats had a palpable tumor by 390 days, compared with 38% of the neophilic. The median life of these neophobic rats was 573 days compared with 850 days for the neophilic sisters. Importantly, temperament did not affect the rate of progression of disease– once a palpable tumor was detected, the rats died at similar rates. However, the age of onset was much earlier in the neophobic animals. Similar results were obtained for pituitary tumors.

The invesitgators then examined the hormone profiles of these rat populations. As the rats progress through puberty (transitioning from irregular to regular cycles), the neophobic rats were twice as likely to experience irregular cycles. In particular, these were marked by a long luteal phase. None of the neophilic animals experienced a prolonged luteal phase. As the animals entered young adulthood, these differences disappeared. However, at 6 months of age, they re-emerged. The females identified as neophobic during infancy began to progress into acyclic estrus. By 9 months 50% of the neophobic animals were entering menopause, compared with just 12% of the neophilic animals.

In contrast, delayed menopause and high estradiol in middle age is associated with greater breast cancer rates in humans. This means that elevated estrogen was probably not responsible for accelerated mortality in the neophobic rats. The authors propose a much more basic mechanism. Based on the early reproductive senescence and the rats’ corticosteroid responses when under stress, the neophobic temperament seems to be associated with accelerated aging in a variety of systems.

Mad Science Mama finds it fascinating that while the behavorial differences fade over time, a neonatal trait predicts life-long differences in hormone profile and health. This work might also help clarify other studies on temperament and patient survival. Such studies have typically focused on the patient’s attitude once a tumor has been diagnosed- earlier behavior traits might in fact be more informative.

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