MALDISTRIBUTION OF INTERSTITIAL NEURONS IN PREFRONTAL WHITE-MATTER OFTHE BRAINS OF SCHIZOPHRENIC-PATIENTS

Background: The cortical subplate is a transitory structure involved i n the formation of connections in developing cerebral cortex. Intersti tial neurons, normally present in subcortical white matter (WM) of the adult brain, have escaped the programmed cell death that eliminates m ost subplate neurons. Previous investigations indicated a maldistribut ion of one population of interstitial neurons in the WM of brains of s chizophrenic patients, suggesting a defect of the subplate during brai n development. Methods: Three histochemically or immunocytochemically defined neuronal populations were studied in WM beneath the middle fro ntal gyrus of 20 schizophrenic patients and 20 matched control subject s. Results: Brains of schizophrenic patients showed significant change s in the distribution of the three neuronal populations: microtubule-a ssociated protein 2 and nonphosphorylated neurofilament-immunoreactive neurons showed a decreased density in superficial WM and an increased density in deeper WM. Nicotinamide adenine dinucleotide phosphate-dia phorase neurons were reduced in superficial WM and showed variable den sities in deeper WM. Thirty-five percent of the brains of schizophreni c patients but no brains of the control subjects showed a maldistribut ion of neurons toward deeper WM with at least two of the three markers . Changes in neuronal distribution were not linked to age, gender, aut olysis time, or subtype of schizophrenia. Conclusions: Selective displ acement of interstitial WM neurons in the frontal lobe of brains of sc hizophrenic patients may indicate alteration in the migration of subpl ate neurons or in the pattern of programmed cell death Both could lead to defective cortical circuitry in the brains of schizophrenic patien ts.