Abnormal synaptic pruning in schizophrenia: Urban myth or reality?

Boksa, Patricia

doi:10.1503/jpn.120007

Cited by 86 publications

(57 citation statements)

References 31 publications

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“…According to the radial unit hypothesis [10], cortical surface area is driven by the number of columnar units, whereas cortical thickness is determined by the number of cells within a column. Some have suggested that postnatal developmental events affecting GM are preferentially reflected in cortical thickness, although this remains largely speculative [11]–[16].…”

Section: Introductionmentioning

confidence: 99%

Anatomical Abnormalities in Gray and White Matter of the Cortical Surface in Persons with Schizophrenia

et al. 2013

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BackgroundAlthough schizophrenia has been associated with abnormalities in brain anatomy, imaging studies have not fully determined the nature and relative contributions of gray matter (GM) and white matter (WM) disturbances underlying these findings. We sought to determine the pattern and distribution of these GM and WM abnormalities. Furthermore, we aimed to clarify the contribution of abnormalities in cortical thickness and cortical surface area to the reduced GM volumes reported in schizophrenia.MethodsWe recruited 76 persons with schizophrenia and 57 healthy controls from the community and obtained measures of cortical and WM surface areas, of local volumes along the brain and WM surfaces, and of cortical thickness.ResultsWe detected reduced local volumes in patients along corresponding locations of the brain and WM surfaces in addition to bilateral greater thickness of perisylvian cortices and thinner cortex in the superior frontal and cingulate gyri. Total cortical and WM surface areas were reduced. Patients with worse performance on the serial-position task, a measure of working memory, had a higher burden of WM abnormalities.ConclusionsReduced local volumes along the surface of the brain mirrored the locations of abnormalities along the surface of the underlying WM, rather than of abnormalities of cortical thickness. Moreover, anatomical features of white matter, but not cortical thickness, correlated with measures of working memory. We propose that reductions in WM and smaller total cortical surface area could be central anatomical abnormalities in schizophrenia, driving, at least partially, the reduced regional GM volumes often observed in this illness.

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Section: Introductionmentioning

confidence: 99%

Anatomical Abnormalities in Gray and White Matter of the Cortical Surface in Persons with Schizophrenia

et al. 2013

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“…These data described here highlight the strong correlation between pruning and schizophrenia. Although a direct association between schizophrenia and mutations in genes with known functions during pruning has been hard to establish, it is interesting that several genes important for calcium signaling and synapse development, stability and refinement have been linked to this neurological disease (Boksa 2012, Schizophrenia Working Group of the Psychiatric Genomics 2014). Taken together, these studies point to developmental circuit refinement as one of the contributing factors to be considered when analyzing the etiology of this debilitating disease.…”

Section: Pruning In Human Development and Disease – The Example Of Scmentioning

confidence: 99%

Sculpting Neural Circuits by Axon and Dendrite Pruning

Riccomagno

Kolodkin

2015

Annu. Rev. Cell Dev. Biol.

287

232

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The assembly of functional neural circuits requires the combined action of progressive and regressive events. Regressive events encompass a variety of inhibitory developmental processes, including axon and dendrite pruning, which facilitate the removal of exuberant neuronal connections. Most axon pruning involves the removal of axons that had already made synaptic connections, thus, axon pruning is tightly associated with synapse elimination. In many instances these developmental processes are regulated by the interplay between neurons and glial cells that act instructively during neural remodeling. Owing to the importance of axon and dendritic pruning, these remodeling events require precise spatial and temporal control, and this is achieved by a range of distinct molecular mechanisms. Disruption of these mechanisms results in abnormal pruning, which has been linked to brain dysfunction. Therefore, understanding the mechanisms of axon and dendritic pruning will be instrumental in advancing our knowledge of neural disease and mental disorders.

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“…Another mechanism incorporating inflammation and microglia with the two-hit and the glutamate hypofunction hypotheses is synaptic pruning (for review, see Hua and Smith, 2004; Schafer and Stevens, 2010; Paolicelli et al, 2011; Chung and Barres, 2012; Boksa, 2012). Pruning is the process by which synapses are culled in an activity dependent manner during late adolescence, essentially preserving high load synaptic connections at the expense of low use, potentially extraneous connections.…”

Section: Mechanismsmentioning

confidence: 99%

Inflammation and the two-hit hypothesis of schizophrenia

Feigenson

Kusnecov

Silverstein

2014

Neuroscience & Biobehavioral Reviews

245

174

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The high societal and individual cost of schizophrenia necessitates finding better, more effective treatment, diagnosis, and prevention strategies. One of the obstacles in this endeavor is the diverse set of etiologies that comprises schizophrenia. A substantial body of evidence has grown over the last few decades to suggest that schizophrenia is a heterogeneous syndrome with overlapping symptoms and etiologies. At the same time, an increasing number of clinical, epidemiological, and experimental studies have shown links between schizophrenia and inflammatory conditions. In this review, we analyze the literature on inflammation and schizophrenia, with a particular focus on comorbidity, biomarkers, and environmental insults. We then identify several mechanisms by which inflammation could influence the development of schizophrenia via the two-hit hypothesis. Lastly, we note the relevance of these findings to clinical applications in the diagnosis, prevention, and treatment of schizophrenia.

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Abnormal synaptic pruning in schizophrenia: Urban myth or reality?

Cited by 86 publications

References 31 publications

Anatomical Abnormalities in Gray and White Matter of the Cortical Surface in Persons with Schizophrenia

Anatomical Abnormalities in Gray and White Matter of the Cortical Surface in Persons with Schizophrenia

Sculpting Neural Circuits by Axon and Dendrite Pruning

Inflammation and the two-hit hypothesis of schizophrenia

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