Selective Loss of Smaller Spines in Schizophrenia.

OBJECTIVE: Decreased density of dendritic spines in adult schizophrenia subjects has been hypothesized to result from increased pruning of excess synapses in adolescence. In vivo imaging studies have confirmed that synaptic pruning is largely driven by the loss of large or mature synapses. Thus, increased pruning throughout adolescence would likely result in a deficit of large spines in adulthood. Here, the authors examined the density and volume of dendritic spines in deep layer 3 of the auditory cortex of 20 schizophrenia and 20 matched comparison subjects as well as aberrant voltage-gated calcium channel subunit protein expression linked to spine loss. METHOD: Primary auditory cortex deep layer 3 spine density and volume was assessed in 20 pairs of schizophrenia and matched comparison subjects in an initial and replication cohort (12 and eight pairs) by immunohistochemistry-confocal microscopy. Targeted mass spectrometry was used to quantify postsynaptic density and voltage-gated calcium channel protein expression. The effect of increased voltage-gated calcium channel subunit protein expression on spine density and volume was assessed in primary rat neuronal culture. RESULTS: Only the smallest spines are lost in deep layer 3 of the primary auditory cortex in subjects with schizophrenia, while larger spines are retained. Levels of the tryptic peptide ALFDFLK, found in the schizophrenia risk gene CACNB4, are inversely correlated with the density of smaller, but not larger, spines in schizophrenia subjects. Consistent with this observation, CACNB4 overexpression resulted in a lower density of smaller spines in primary neuronal cultures. CONCLUSIONS: These findings require a rethinking of the overpruning hypothesis, demonstrate a link between small spine loss and a schizophrenia risk gene, and should spur more in-depth investigations of the mechanisms that govern new or small spine generation and stabilization under normal conditions as well as how this process is impaired in schizophrenia.

The protective effects of neighborhood collective efficacy on British children growing up in deprivation: a developmental analysis.

This article reports on the influence of neighborhood-level deprivation and collective efficacy on children's antisocial behavior between the ages of 5 and 10 years. Latent growth curve modeling was applied to characterize the developmental course of antisocial behavior among children in the E-Risk Longitudinal Twin Study, an epidemiological cohort of 2,232 children. Children in deprived versus affluent neighborhoods had higher levels of antisocial behavior at school entry (24.1 vs. 20.5, p < .001) and a slower rate of decline from involvement in antisocial behavior between the ages of 5 and 10 (-0.54 vs. -0.78, p < .01). Neighborhood collective efficacy was negatively associated with levels of antisocial behavior at school entry (r = -.10, p < .01) but only in deprived neighborhoods; this relationship held after controlling for neighborhood problems and family-level factors. Collective efficacy did not predict the rate of change in antisocial behavior between the ages of 5 and 10. Findings suggest that neighborhood collective efficacy may have a protective effect on children living in deprived contexts.