Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia

Abstract

Objective-A pilot study of the density of dendritic spines on pyramidal neurons in layer III of human temporal and frontal cerebral neocortex in schizophrenia. Methods-Postmortem material from a group of eight prospectively diagnosed schizophrenic patients, five archive schizophrenic patients, 11 nonschizophrenic controls, and one patient with schizophrenia-like psychosis, thought to be due to substance misuse, was impregnated with a rapid Golgi method. Spines were counted on the dendrites of pyramidal neurons in temporal and frontal association areas, of which the soma was in layer III (which take part in corticocortical connectivity) and which met strict criteria for impregnation quality. Altogether 25 blocks were studied in the schizophrenic group and 21 in the controls. If more than one block was examined from a single area, the counts for that area were averaged. All measurements were made blind: diagnoses were only disclosed by a third party after measurements were completed. Possible confounding aVects of coexisiting Alzheimer's disease were taken into account, as were the eVects of age at death and postmortem interval. Results-There was a significant (p<0.001) reduction in the numerical density of spines in schizophrenia (276/mm in control temporal cortex and 112/mm in schizophrenic patients, and 299 and 101 respectively in the frontal cortex). An analysis of variance, taking out eVects of age at death and postmortem interval, which might have explained the low spine density for some of the schizophrenic patients, did not aVect the significance of the results. Conclusion-The results support the concept of there being a defect in the fine structure of dendrites of pyramidal neurons, involving loss of spines, in schizophrenia and may help to explain the loss of cortical volume without loss of neurons in this condition, although the eVect of neuroleptic drugs cannot be ruled out. (J Neurol Neurosurg Psychiatry 1998;65:446-453)

Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine

“…In fact, a recent study has demonstrated a strong correlation between the loss of asymmetric spine synapses in monkey PFC and cognitive impairment during aging (Peters et al, 2008). Several groups have reported dystrophic changes in frontal cortical pyramidal cell dendrites in schizophrenia, including decreases in dendritic length, branching, and spine density (Black et al, 2004;Broadbelt et al, 2002;Garey et al, 1998;Glantz and Lewis, 2000;Kalus et al, 2000;Kolluri et al, 2005), consistent with the hypothesis that these changes are involved in the cognitive dysfunction that typifies the disorder. It is not currently known though whether the pathological changes in the cortex in schizophrenia are fixed or can be altered by treatment with antipsychotic drugs.…”

Paracetamol Overdose Induces Physiological and Pathological Aberrations in Rat Brain

“…A link between abnormal neural spines and mental retardation was suggested for first time by (Purpura 1974). Also, mental disorders such as schizophrenia is associated with decreased density of dendritic spines in neocortical pyramidal neurons (Garey et al, 1998). In addition, patients with Down syndrome have a decreased spine density in neocortex (Takashima et al, 1989) and hippocampus (Ferrer and Gullotta 1990).…”

Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients

“…Animal models in which GSH levels are decreased show hypofunction of NMDA receptors (Steullet et al, 2006). During development, the transitory decrease of GSH levels in conjunction with an increase in dopamine result in morphological (Cabungcal et al, 2006;Gheorghita et al, 2007, unpublished work) and behavioral (Cabungcal et al, 2007;Castagné et al, 2004a, b) impairments in animals that are similar to those observed in schizophrenia (Garey et al, 1998;Glantz and Lewis, 2000;Kolluri et al, 2005;Robbins, 2005). Several studies have demonstrated that the administration of NMDA receptor antagonists, such as phencyclidine or ketamine, induces in control subjects symptoms that are similar to those observed in schizophrenia and exacerbates these symptoms in patients (Krystal et al, 1994).…”