2 Neuroscience2.8 Modulators, hormones and inflammatory responses

2.8.3 Main hormonal and neuroendocrine changes in psychiatric disorders

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Written by Resident Doctor Committee · Published

The hypothalamic-pituitary-adrenal axis

  • Corticotrophin-releasing hormone (CRH) from the paraventricular hypothalamus drives pituitary adrenocorticotrophic hormone (ACTH), which drives adrenal cortisol.

  • Cortisol limits its own release by negative feedback.

Follow the arrows from hypothalamic CRH to pituitary ACTH to adrenal cortisol. The bar-ended lines show cortisol switching off its own release by negative feedback at the hypothalamus and the pituitary. Biolinkage Project, CC BY-SA 4.0, via Wikimedia Commons

The axis in depression

  • Depression shows hypothalamic-pituitary-adrenal (HPA) axis hyperactivity driven by raised hypothalamic CRH, with raised ACTH and cortisol downstream.

  • The ACTH response to a CRH challenge is blunted.

  • HPA hyperactivity with raised cortisol is also found in bipolar affective disorder.

  • Impaired negative feedback shows as cortisol non-suppression on the dexamethasone suppression test and a raised late-evening cortisol trough, which flattens the diurnal rhythm.

  • Cortisol dysregulation rises with severity and acuity, not chronicity.

  • It is most consistent in melancholic and psychotic depression and lower in atypical depression, and many depressed people have normal cortisol.

The dexamethasone suppression test

  • The test gives dexamethasone 1 mg at 11 pm and measures cortisol the next day.

  • About 40 to 50% of melancholic cases fail to suppress, more in psychotic depression, and results often normalise after recovery.

  • Non-suppression is not specific to mood disorders: it also occurs in underweight anorexia nervosa, dementia, alcohol use and Cushing's syndrome.

  • Poor sensitivity and specificity keep it out of diagnostic use.

Post-traumatic stress disorder

  • Post-traumatic stress disorder paradoxically shows lower cortisol through enhanced glucocorticoid negative feedback, with exaggerated suppression on dexamethasone.

Feedback separates the two: weak in depression (non-suppression), strong in post-traumatic stress disorder (exaggerated suppression).

Melatonin

  • The pineal gland synthesises and secretes melatonin, which it makes from serotonin.

  • The suprachiasmatic nucleus only times its release to the biological night, and light reaching the retina suppresses it.

Other axes

Axis

Main change

Thyroid

A quarter to a third of depressed people show a blunted thyroid-stimulating hormone response to thyrotrophin-releasing hormone; hypothyroidism can mimic depression

Prolactin

Antipsychotic D2 blockade raises prolactin (risperidone, amisulpride); aripiprazole tends to lower it

Leptin

Low in restrictive eating disorders; high with central resistance in obesity

Revision material for the MRCPsych examinations. Not clinical guidance, and not for use in patient care.