Contrasting neuroendocrine responses in depression and chronic fatigue syndrome, 1995, Cleare et al

[forestglip]

Contrasting neuroendocrine responses in depression and chronic fatigue syndrome

Spoiler: Authors

Cleare, Anthony J.; Bearn, Jenny; Allain, Teresa; McGregor, Alan; Wessely, Simon; Murray, Robin M.; O'Keane, Veronica

Abstract
Hypothalamic-pituitary-adrenal (HPA) axis and central 5-HT function were compared in chronic fatigue syndrome (CFS), depression and healthy states. 10 patients with CFS and 15 patients with major depression were matched for age, weight, sex and menstrual cycle with 25 healthy controls.

Baseline-circulating cortisol levels were highest in the depressed, lowest in the CFS and intermediate between the two in the control group (P = 0.01). Prolactin responses to the selective 5-HT-releasing agent d-fenfluramine were lowest in the depressed, highest in the CFS and intermediate between both in the healthy group (P = 0.01).

Matched pair analysis confirmed higher prolactin responses in CFS patients than controls (P = 0.05) and lower responses in depressed patients than controls (P = 0.003). There were strong inverse correlations between prolactin and cortisol responses and baseline cortisol values.

These data confirm that depression is associated with hypercotisolaemia and reduced central 5-HT neurotransmission and suggest that CFS may be associated with hypocortisolaemia and increased 5-HT function. The opposing responses in CFS and depression may be related to reversed patterns of behavioural dysfunction seen in these conditions. These findings attest to biological distinctions between these disorders.

Web | DOI | Journal of Affective Disorders | Paywall

 

[forestglip]

This is one of the studies finding an increased prolactin response in ME/CFS. I figured these studies are important enough to have their own threads, and to be able to discuss little details without cluttering the main prolactin response thread.

This study also found decreased baseline cortisol in ME/CFS and increased baseline cortisol in depression.

Baseline cortisol (CORT) varied amongst the groups being highest in the depressed (428 & 53.1 nmol/l), lowest in the CFS (226 + 35.6 nmol/l) and intermediate between the two in the control (305 f 21.4 nmol/l) group (F2,37= 5.12, P = 0.01).

Here's the plot showing cortisol level after administration of 30 mg oral d-fenfluramine. The lowest line is ME/CFS, the middle line is controls, and the highest line is depression.


Interestingly, for baseline, they chose to use the values 1 hour after administration of d-fenfluramine:

The decline in hormone concentrations that occurred at 1-h represented recovery from the stress response to cannulation and natural circadian falls and, thus, 1-h values were taken as a more accurate baseline.

If looking at 0 hours, the cortisol level looks about the same in ME/CFS and controls. I wonder how they can know that the difference at 1 hour isn't related to the fenfluramine.

Also, while the p-value above for baseline cortisol differences was significant, it was comparing all three groups at once to test the null hypothesis that all groups are equal. If only the depression group had high cortisol, that could have made it significant. The comparison of ME/CFS with just their matched controls was not significant:

Mean diff[baseline CORT] was - 47 nmol/l (95% CI - 148-54; NS)

 

[forestglip]

Copying this quote that notes that for the prolactin and cortisol tables, the titles and references to them are swapped, and other notes about the study:

Just eyeballing the CFS vs Controls rows the groups are not actually all that different compared to the buspirone studies:

(Yes this table says Cortisol. I am foggy but 90% sure they labelled their prolactin and cortisol tables backwards -- this is the table whose data matches the prolactin graph ME/CFS Science Blog posted earlier.)

Anyway, just a lot of words to say buspirone seems potentially more interesting than d-fenfluramine. I wonder, assuming buspirone really does have a significant effect and d-fenfluramine doesn't, if we can get any clue from that about what is happening here.

 

[forestglip]

No idea if this can affect anything, but just noting:

A standard light snack was served after 1 h.

​