Markers of Glutamate Synaptic Transmission and Plasticity Are Increased in the Anterior Cingulate Cortex in Bipolar Disorder

Background: Cortical glutamate levels are elevated in bipolar disorder, but the interpretation of this increase is unclear because glutamate has metabolic as well as neurotransmitter roles. We investigated this by measuring vesicular glutamate transporter 1 (VGluT1) expression, which reflects activity at glutamate synapses. We also measured netrin-G1 and netrin-G2 messenger RNAs because these genes are involved in the formation and plasticity of glutamatergic connections. Methods: Using quantitative polymerase chain reaction, we quantified transcripts for VGluT1, netrin-G1 (isoforms G1c, G1d, and G1f), and netrin-G2 in the anterior cingulate cortex from subjects with bipolar disorder (n = 34), schizophrenia (n = 35), and healthy control subjects (n = 35). Results: Vesicular glutamate transporter 1, netrin-G2, and netrin-G1d and G1f were increased in bipolar disorder but not in schizophrenia. Netrin-G1c did not differ between groups. Netrin-G 1 c and netrin-G1f expression showed left-right asymmetries. Vesicular glutamate transporter 1 messenger RNA correlated with brain weight. Conclusions: Increased VGluT1 expression is supportive of elevated glutamate neurotransmission in the anterior cingulate cortex in bipolar disorder. The netrin-G1 and netrin-G2 findings suggest there may be an underlying difference in the plasticity of the affected circuitry.