The reduction in cortical GM and WM volumes and distinct WM tract disturbances in TRS may be a consequence of disrupted macro-scale neural architecture and network dysconnectivity that originate within distinct micro-scale neuronal ensembles. Morphometric studies that have been investigated in schizophrenia suggest that cortical volume loss is not related to the reduction of the number of neurons in the cortex, but to architectural neuronal disorganization, reduction in neuronal size, and diminished neuropil (axons, dendrites, and synaptic terminals) (65, 66). The etiology behind the loss of dendritic spines and dendritic length of cortical pyramidal neurons is not entirely clear but may originate from hypofunctioning NMDA glutamate receptors on pyramidal cells and interneurons (67–69). From a circuit perspective, hypofunction of NMDA receptors on GABAergic inhibitory interneurons disinhibits associated pyramidal neurons in the circuit and causes a potentially pathological glutamatergic excitatory effect (70, 71).