Although, the pathogenetic mechanisms of schizophrenia, bipolar disorder, and major depression are not clearly understood, various neurotransmitter systems are reported to have altered expression patterns of their receptor and transporter proteins. Changes in the expression of the neutral amino acid transporter 1 (ASCT-1) protein in the anterior cingulate gyrus and the hippocampus were investigated using immunohistochemistry and western blotting. A significant decrease in ASCT-1 immunoreactivity in neurons in the cingulate cortex as well as astrocytes of the white matter was seen in schizophrenia. In bipolar disorder and major depression, similar results were seen for neurons. In the hippocampus, there was a striking loss of immunoreactivity on astrocytes, neurons and interneurons in multiple regions in schizophrenia and bipolar disorder, while only minor changes were seen in major depression. The altered expression of ASCT-1 in neurons and astrocytes reflects profound changes in glutamatergic neurotransmission and highlights a significant role of astrocytes in the pathophysiology of neurotransmission in these major psychiatric disorders.