Schizophrenia; from structure to function with special focus on the mediodorsal thalamic prefrontal loop

Objective: To describe structural and biochemical evidence from postmortem brains that implicates the reciprocal connections between the mediodorsal thalamic nucleus and the prefrontal cortex in cognitive symptoms of schizophrenia. Method: The estimation of the regional volumes and cell numbers was obtained using stereological methods. The biochemical analyses of molecular expression in postmortem brain involve quantitative measurement of transcripts and proteins by in-situ (RNA) or Western blot/autoradiography in brains from patients with schizophrenia and comparison subjects. Results: Stereological studies in postmortem brain from patients with schizophrenia have reported divergent and often opposing findings in the total number of neurons and volume of the mediodorsal (MD) thalamic nucleus, and to a lesser degree in its reciprocally associated areas of the prefrontal cortex. Similarly, quantitative molecular postmortem studies have found large inter-subject and between-study variance at both the transcript and protein levels for receptors and their interacting molecules of several neurotransmitter systems in these interconnected anatomical regions. Combined, large variation in stereological and molecular studies indicates a complex and heterogeneous involvement of the MD thalamic-prefrontal loop in schizophrenia. Conclusion: Based on a considerable heterogeneity in patients suffering from schizophrenia, large variation in postmortem studies, including stereological and molecular postmortem studies of the MD thalamus and frontal cortex, might be expected and may in fact partly help to explain the variable endophenotypic traits associated with this severe psychiatric illness.