A pilot investigation of differential neuroendocrine associations with fronto-limbic activation during semantically-cued list learning in mood disorders

J Affect Disord. 2018 Oct 15;239:180-191. doi: 10.1016/j.jad.2018.07.006. Epub 2018 Jul 7.


Background: Decreased volume and disrupted function in neural structures essential for memory formation (e.g. medial temporal lobe and prefrontal cortex) are common among individuals with depression. Hypothalamic-pituitary-axis function, as reflected by measurement of cortisol levels, is linked to neural activity during memory encoding in healthy people. However, it is not as well understood whether cortisol is associated with alterations in fronto-temporal recruitment during memory encoding in depression.

Methods: In this pilot study, we evaluated associations between cortisol and neural activation during memory encoding in 62 adults (18-65 years) with mood disorders (MD; n = 39, 66.7% female), including major depression (n = 28) and bipolar I disorder (n = 11), and healthy controls (HC; n = 23, 43.5% female). Participants provided salivary cortisol samples before and after completing a semantically-cued list-learning task during 3-Tesla fMRI. Links between pre-scan cortisol (and cortisol change) and activation during encoding were evaluated using block and event-related models.

Results: Overall, pre-scan cortisol level was positively associated with greater engagement of fronto-limbic activation during the encoding block. However, in MD, pre-scan cortisol was associated with attenuated activation during encoding in medial frontal, superior and middle temporal gyri, insula, lingual gyrus, and claustrum relative to HCs. Cortisol-related attenuation of activation in MD was also observed during encoding of words subsequently recalled in the ventral anterior cingulate, hypothalamus, and middle temporal gyrus. By and large, cortisol change (pre/post scan) predicted the same pattern of findings in both block and event-related contrasts.

Limitations: Although analyses accounted for variations in scanner time of day, circadian alterations in cortisol may have introduced variability into the results.

Conclusions: Pre-scan cortisol may selectively interfere with recruitment of important fronto-temporal memory circuitry in mood disorders. The inverted associations between cortisol and neural function in MD relative to HC also elucidate potentially unique pathophysiological markers of mood disorders.

Keywords: Cortisol; Functional imaging; Memory; Mood disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Association Learning*
  • Bipolar Disorder / diagnostic imaging
  • Bipolar Disorder / metabolism
  • Bipolar Disorder / physiopathology
  • Bipolar Disorder / psychology*
  • Brain / diagnostic imaging*
  • Brain / physiopathology
  • Case-Control Studies
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiopathology
  • Cues
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / psychology*
  • Female
  • Functional Neuroimaging
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / physiopathology
  • Humans
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Memory
  • Middle Aged
  • Mood Disorders / diagnostic imaging
  • Mood Disorders / metabolism
  • Mood Disorders / physiopathology
  • Mood Disorders / psychology
  • Pilot Projects
  • Pituitary-Adrenal System / metabolism
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / physiopathology
  • Saliva / chemistry
  • Semantics
  • Temporal Lobe / diagnostic imaging
  • Temporal Lobe / physiopathology
  • Young Adult


  • Hydrocortisone