Dendritic spine alterations in schizophrenia

Abstract

Schizophrenia is a chronic illness affecting approximately 0.5–1% of the world’s population. The etiology of schizophrenia is complex, including multiple genes and contributing environmental effects that adversely impact neurodevelopment. Nevertheless, a final common result, present in many subjects with schizophrenia, is impairment of pyramidal neuron dendritic morphology in multiple regions of the cerebral cortex. In this review we summarize the evidence of reduced dendritic spine density and other dendritic abnormalities in schizophrenia, evaluate current data that informs the neurodevelopment timing of these impairments, and discuss what is known about possible upstream sources of dendritic spine loss in this illness.

Gray Matter Neuritic Microstructure Deficits in Schizophrenia and Bipolar Disorder

“…Therefore, deficits in dendritic density, axonal density or both may explain the NDI deficit we observed in the hippocampus, temporal pole, and parahippocampal cortices in schizophrenia. Although conflicting findings have been reported (13), our findings of decreased hippocampal and parahippocampal neuritic density are congruent with the results of neuropathological studies of schizophrenia indicating lower microtubuleassociated protein-2 (MAP2, a cytoskeletal protein primarily located in dendrites and cell bodies) immunoreactivity mainly in hippocampus and associated areas (5,13,52). Other post-mortem studies have suggested lower prefrontal (11) and temporal(10) dendritic spine density in schizophrenia.…”

“…Although it has not been investigated as thoroughly, similar deficits in MAP2, dendritic spine density, and dendritic length have been reported in bipolar disorder (11,12). However, conflicting observations, limited number of brain regions examined, small sample sizes and potential alterations during the postmortem-interval prior to tissue fixation can limit interpretation of postmortem studies (2,13). In vivo neuroimaging of these neural substrates could provide opportunity for new knowledge of the neurobiological underpinnings of severe mental illnesses.…”

Auditory Cortex Characteristics in Schizophrenia: Associations With Auditory Hallucinations

“…One of the most consistent postmortem finding in schizophrenia is reduced dendritic spine density, which has been found in several cortical regions. 47 It has been suggested that excessive pruning during adolescence may cause the dendritic spine loss. 47 Reduced somal size of pyramidal neurons and reduced density of dendrites and axon terminals in cortical layer 3 has been demonstrated in the primary auditory cortex and the auditory association cortex in schizophrenia.…”

“…47 It has been suggested that excessive pruning during adolescence may cause the dendritic spine loss. 47 Reduced somal size of pyramidal neurons and reduced density of dendrites and axon terminals in cortical layer 3 has been demonstrated in the primary auditory cortex and the auditory association cortex in schizophrenia. [48][49][50] Pyramidal neurons in layer 3 in the sensory cortex are involved in feedforwarding sensory signals to higher cortical areas.…”

Matrix Metalloproteinase-9 as a Novel Player in Synaptic Plasticity and Schizophrenia: Table 1.

“…39,40 Another hallmark of schizophrenia is the dysfunction of dendritic spines. Several studies reported a reduction of spine density in cortical pyramidal neurons in schizophrenia (for review, see Moyer et al 41 ). Interestingly, ultrastructural studies by Roberts et al 42 demonstrated an approximately 30% reduction of striatal spine size in schizophrenia patients compared with the control population.…”