Could glutamate spectroscopy differentiate bipolar depression from unipolar?

BACKGROUND: Accurate differentiation of bipolar and unipolar depression is a key clinical challenge. A biological measure that could differentiate bipolar and unipolar depression might supplement clinical assessment. Magnetic Resonance Spectroscopy measurements of total glutamate and glutamine (Glx) in anterior cingulate cortex are one potential measure. The objective of this study was to assess the potential performance of this measure. METHODS: Meta-analysis of data from eleven studies where anterior cingulate Glx of depressed patients has been compared to that of healthy controls was performed. Effect sizes for bipolar and unipolar depression were calculated as Standardised Mean Differences. The best estimate of test classification performance on the basis of observed effects was calculated. RESULTS: People with unipolar depression had on average lower levels of Glx than healthy controls (effect size -1.05; 95% CI -058 to -1.53). People with bipolar depression tended towards higher Glx than healthy controls (effect size 0.40; 95% CI -0.04 to 0.85). This yielded a difference in Glx between unipolar and bipolar depression of effect size 1.46 (95% CI 0.80-2.11). Based on this difference, a test differentiating bipolar from unipolar depression by whether Glx was higher or lower than the average in healthy population would have sensitivity 0.66 and specificity 0.85. LIMITATIONS: There is an absence of studies directly comparing unipolar and bipolar depressed patients. CONCLUSIONS: On available data, measurement of anterior cingulate Glx is a promising potential tool for differentiation of bipolar and unipolar depression. This potential effect requires direct validation within mixed clinical cohorts.