Salivary levels of the endogenous neuromodulator kynurenic acid (KYNA) can identify patients with schizophrenia who are intolerant of stress, research shows.
“Importantly, we have uncovered a potential biomarker separating a subgroup of patients with schizophrenia displaying a particular maladaptive behaviour”, say lead study author Joshua Chiappelli (Maryland Psychiatric Research Center, Baltimore, USA) and colleagues.
The 64 schizophrenia patients in the study were significantly more often distress intolerant than the 64 mentally healthy controls, who were matched for age, gender and smoking status. Both groups undertook two computer-based tasks (the Paced Auditory Serial Addition Task and the Mirror-Tracing Persistence Task), which were difficult enough to induce some participants to quit, despite the promise of a monetary reward for persistence.
Nearly 40% of the schizophrenia patients quit both tasks, compared with less than 20% of the controls, the team reports in JAMA Psychiatry.
Patients had higher baseline KYNA levels than controls, at 7.40 versus 6.02 nM, and the stressful tasks caused a transient increase to a similar extent in both groups. Among distress tolerant participants (those who completed at least one task), the pattern of KYNA change was similar in patients and controls.
However, among the distress intolerant participants, the schizophrenia patients had a significantly more pronounced increase in KYNA levels than the controls. In controls, levels started at about 5 mM and rose to about 8 nM when measured 20 minutes after undertaking the tasks; the corresponding measurements in patients were about 11 and 15 nM.
Of note, these differences were not explained by participants’ subjective experiences. Negative affect on the Positive and Negative Affect Schedule was significantly higher in the schizophrenia patients than the controls before and after stress, but the stress-induced change was similar for the two groups and the magnitude of change in KYNA levels did not correlate with the change in negative affect.
In an accompanying editorial, Daniel Javitt (Columbia University College of Physicians and Surgeons, New York, USA) highlights the finding that “patients may be more stressed than controls, even by simple tasks such as mental arithmetic or mirror drawing.”
He says: “This must be taken into account when asking patients to participate in other mentally demanding activities, such as cognitive remediation or supported employment.”
He adds that monitoring salivary KYNA levels could help to identify patients prone to react badly to stress who may benefit from supportive therapy.
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