Review: A systematic review of hypothalamic-pituitary-adrenal axis function in schizophrenia: implications for mortality

Abstract

There is convincing evidence that environmental stress plays a significant role in modifying both mental and physical health. The biological mechanisms linking stress to ill health are not fully understood, but significant evidence points to a central role of the stress axes; the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system. Together these two systems link the brain and the body and are crucial in maintaining homeostasis as well as improving an organism’s survival chances in the face of environmental challenge. There is evidence of altered HPA axis function in people with a range of mental disorders, and this may in part explain the poor physical health of people with psychotic, mood and anxiety disorders. This paper systematically reviews HPA axis function in people with schizophrenia and relates this to the pattern of physical health seen in this disease. In summary, the evidence suggests people with schizophrenia can experience both hyper- and hypo-function of the HPA axis. It is likely that this contributes to the pattern of poor physical health and premature mortality suffered by people with schizophrenia, in particular the high rates of cardiovascular and metabolic disturbance.

Hair cortisol in drug-naïve first-episode individuals with psychosis

“…Previous studies have found correlations between PANSS subscales and blood cortisol even in the absence of differences between the cortisol levels of patients and controls. 28,31 Taken together, these data suggest that the dynamics of cortisol concentration over time might be more important than the concentrations per se in predicting psychopathology.…”

Biomarkers and schizophrenia: a qualitative review

“…A longitudinal study conducted in FEP patients showed that those who did not respond to 12-week antipsychotic treatment already had at illness onset a significant lower CAR (measured in the saliva) compared with patients who responded [72]. It was observed that at psychosis onset CAR predicts subsequent treatment response, as blunted CAR shown a tendency to remain unchanged with antipsychotic treatment [75]. On the whole, it is possible that more blunted CAR can possibly be a trait marker, reflecting a more severe illness not modifiable by treatment [33,72,75].…”

The "selfish brain" hypothesis for metabolic abnormalities in bipolar disorder and schizophrenia

“…66 The stress response system plays an important role in brain energy metabolism by increasing the availability of Patients with schizophrenia present long periods of increased cortisol secretion, especially those experiencing their first episode and not previously treated. 67 They also show low reactivity to stress, with a blunted cortisol response to psychosocial stress. 67 In BD, studies have shown altered corticotropin-releasing hormone (CRH) secretion previous to symptom onset, 68 cortisol hypersecretion in euthymia, depression and mania, 69 and a non-normalization of the HPA axis after symptom remission.…”

“…67 They also show low reactivity to stress, with a blunted cortisol response to psychosocial stress. 67 In BD, studies have shown altered corticotropin-releasing hormone (CRH) secretion previous to symptom onset, 68 cortisol hypersecretion in euthymia, depression and mania, 69 and a non-normalization of the HPA axis after symptom remission. 70 Overall, evidence points to disturbances of the stress response system as a trait of both illnesses.…”