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Abnormal cholinergic neurotransmission has been suggested to occur in psychiatric illness. Therefore, this study investigated cholinergic muscarinic receptors in the anterior cingulate cortex (ACC) of schizophrenia, bipolar disorder and major depression disorder (n = 15 per group). We used quantitative autoradiography to measure [³H]pirenzepine binding to M1 and M4 receptors. Brain tissue was obtained from the Stanley Foundation Neuropathology Consortium. [³H]pirenzepine binding was higher in superficial laminae (I-II) than in deep laminae (Ill-VI) of the ACC. There was a significant 24% reduction in the density of [³H]pirenzepine in the deep laminae and a significant 19% reduction in the upper laminae of the ACC in the schizophrenia group compared to the control group. There were no differences in [³H]pirenzepine binding in any laminae of the ACC in the bipolar or major depression groups compared with the control group, except for a trend towards decreased [³H]pirenzepine binding in subjects with major depression relative to control subjects. We also detected a significant effect of suicide on [³H]pirenzepine binding in the ACC in subjects who died as a result of suicide relative to those who did not, which was more evident in patients with schizophrenia. A significant effect of the onset of the disease was also observed that was more evident in patients with bipolar disorder. The study provides evidence of decreased muscarinic receptor density in the ACC in schizophrenia but no evidence for significant changes in these receptors in the bipolar and major depression groups. The changes observed in schizophrenia may contribute to dysfunctional ACC neural circuits. [ABSTRACT FROM AUTHOR]

The anterior cingulate cortex is a brain area of potential importance to our understanding of the pathophysiology of schizophrenia. Previous studies suggest abnormalities in the glutamatergic neurotransmission in the anterior cingulate cortex in schizophrenia patients. In the present study we used quantitative autoradiography to investigate the binding of [3H]MK801, [3H]L-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and [3H]kainate, which respectively label the N-methyl-D-aspartate (NMDA), AMPA, and kainate receptors of the ionotropic glutamate receptor family, in the left anterior cingulate cortex of 10 schizophrenia patients and 10 controls, matched for age, gender, and postmortem interval.AMPA receptor densities were higher in cortical layer II, whereas NMDA receptor densities were higher in cortical layers II–III in the anterior cingulate cortex of both control and schizophrenia group. In contrast, kainate receptors displayed the highest density in cortical layer V. [3H]AMPA binding was significantly increased by 25% in layer II in the schizophrenia group as compared with the control group. Similarly, a significant 17% increase of [3H]MK801 binding was observed in layers II–III in the schizophrenia group. No statistically significant difference was observed for [3H] kainate binding between the schizophrenia and control groups.These results suggest that ionotropic glutamate receptors are differentially altered in the anterior cingulate region in schizophrenia. The increase in [3H]AMPA and [3H]MK801 binding in the superficial layers suggests a postsynaptic compensation for impaired glutamatergic neurotransmission in the anterior cingulate cortex in schizophrenia. The findings add to a growing body of literature that supports a dysfunction of excitatory activity in the anterior cingulate cortex in schizophrenia. [Copyright &y& Elsevier]