Depressive Symptoms and Brain Metabolite Alterations in Subjects at Ultra-high Risk for Psychosis: A Preliminary Study

Abstract

Objective: Recent neuroimaging studies have suggested that brain changes occur in subjects at ultra-high risk (UHR) for psychosis while experiencing prodromal symptoms, among which depression may increase the risk of developing a psychotic disorder. The goal of this study is to examine brain metabolite levels in the anterior cingulate cortex, the left dorsolateral prefrontal cortex and the left thalamus in subjects at UHR for psychosis and to compare brain metabolite levels between the UHR subjects with comorbid major depressive disorder and healthy controls.

Methods: Proton magnetic resonance spectroscopy was used to examine brain metabolite levels. Twenty UHR subjects and 20 age- and intelligence quotient (IQ)-matched healthy controls were included in this study.

Results: Overall, no significant differences were observed in any metabolite between the UHR and healthy control group. However, UHR subjects with major depressive disorder showed significantly higher myo-inositol (Ins) levels in the left thalamus, compared to the healthy control.

Conclusion: Our results demonstrate that increased thalamic Ins level is associated with prodromal depressive symptoms. Further longitudinal follow-up studies with larger UHR sample sizes are required to investigate the function of Ins concentrations as a biomarker of vulnerability to psychosis.

Keywords: Depression; Magnetic resonance spectroscopy; Schizophrenia; Ultra-high risk.

FIGURE 1

Location of volumes of interest (VOIs) for magnetic resonance spectroscopy and their sample spectra. A: The anterior cingulate cortex. B: The left dorsolateral prefrontal cortex. C: The left thalamus.

FIGURE 2

Absolute concentrations of myo-inositol in the left thalamus among the UHR group with MDD, those without MDD, and control group. ^*p=0.021. UHR: ultra-high risk, MDD: major depressive disorder.