Cortisol awakening response and negative emotionality linked to asymmetry in major limbic fibre bundle architecture

Psychiatry Res. 2012 Jan 30;201(1):63-72. doi: 10.1016/j.pscychresns.2011.07.015. Epub 2012 Jan 30.


The limbic system plays an important role in regulating the hypothalamic-pituitary-adrenal (HPA) axis as well as aspects of emotion, and both neuroendocrine disturbance and increased negative emotionality are associated with risk for developing affective disorders. However, the extent to which the architecture of connections between limbic structures may be linked to individual differences in basal HPA-axis reactivity and negative emotionality is unknown. Here we tested the hypotheses that microstructural asymmetry of the major limbic fibre bundles would be associated with cortisol awakening response (CAR) and neuroticism, a personality trait associated with the tendency to experience negative emotions. Sixty-nine healthy adults were studied with diffusion-weighted imaging, and fractional anisotropy (FA) was extracted from the cingulum and uncinate fasciculus. Higher neuroticism scores, which were associated with higher CAR, were also correlated with higher right relative to left cingulum FA. Elevated CAR was associated with the degree of FA asymmetry within both the cingulum and the uncinate fasciculus, but in opposing directions. These results suggest that the balance between left- and right-sided limbic circuits may bear an important relationship to hypothalamic-pituitary-adrenal axis reactivity, and to the tendency to experience negative emotions, and they raise important questions about the significance of limbic system architecture.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anisotropy
  • Brain / physiology*
  • Diffusion Magnetic Resonance Imaging
  • Emotions / physiology*
  • Female
  • Functional Laterality / physiology*
  • Humans
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / physiology
  • Image Processing, Computer-Assisted
  • Limbic System / physiology*
  • Male
  • Middle Aged
  • Personality
  • Pituitary-Adrenal System / physiology
  • Saliva / metabolism
  • Wakefulness / physiology*


  • Hydrocortisone