Influence of social cognition as a mediator between cognitive reserve and psychosocial functioning in patients with first episode psychosis.

BACKGROUND: Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. METHODS: The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. RESULTS: At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (-10.215 to -0.337) and (-4.731 to -0.605) respectively). CONCLUSIONS: Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.

"Arrested development". Immature, but not recently generated, neurons in the adult brain.

After the division of neuronal precursors, many of the newly generated cells become immature neurons, which migrate to their final destination in the nervous system, extend neurites and make appropriate connections. For most neurons these events occur in a narrow time window and, once in their definitive location, they immediately start the final stages of their differentiation program, remaining immature only for a short time. The main objective of this review is to present and discuss recent data on a peculiar population of cells in the adult brain, which retain an immature neuronal phenotype for an unusually prolonged time. We review and discuss recent evidence on the temporal and spatial origin of these cells, their distribution in rodents and other mammals, their structure and neurochemical phenotype, and their putative fate and function. The review is mainly focused on the population of immature neurons located in the layer II of certain cortical regions, but we will also describe similar populations found in other regions of the peripheral and central nervous systems.

Divergent impact of the polysialyltransferases ST8SiaII and ST8SiaIV on polysialic acid expression in immature neurons and interneurons of the adult cerebral cortex.

Polysialic acid (PSA) is a negatively charged carbohydrate polymer, which confers antiadhesive properties to the neural cell adhesion molecule NCAM and facilitates cellular plasticity during brain development. In mice, PSA expression decreases drastically during the first postnatal weeks and it gets confined to immature neurons and regions displaying structural plasticity during adulthood. In the brain, PSA is exclusively synthesized by the two polysialyltransferases ST8SiaII and ST8SiaIV. To study their individual contribution to polysialylation in the adult, we analyzed PSA expression in mice deficient for either polysialyltransferase. Focusing on the cerebral cortex, our results indicate that ST8SiaIV is solely responsible for PSA expression in mature interneurons and in most regions of cortical neuropil. By contrast, ST8SiaII is the major polysialyltransferase in immature neurons of the paleocortex layer II and the hippocampal subgranular zone. The numbers of cells expressing PSA or doublecortin, another marker of immature neurons, were increased in the paleocortex layer II of ST8SiaIV-deficient mice, indicating altered differentiation of these cells. Analysis of doublecortin expression also indicated that the production of new granule neurons in the subgranular zone of ST8SiaII-deficient mice is not affected. However, many of the immature granule neurons showed aberrant locations and morphology, suggesting a role of ST8SiaII in their terminal differentiation.

Effects of chronic fluoxetine treatment on the rat somatosensory cortex: activation and induction of neuronal structural plasticity.

Recent hypotheses support the idea that disruption of normal neuronal plasticity mechanisms underlies depression and other psychiatric disorders, and that antidepressant treatment may counteract these changes. In a previous report we found that chronic fluoxetine treatment increases the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a molecule involved in neuronal structural plasticity, in the somatosensory cortex. In the present study we intended to find whether, in fact, cell activation and neuronal structural remodeling occur in parallel to changes in the expression of this molecule. Using immunohistochemistry, we found that chronic fluoxetine treatment caused an increase in the expression of the early expression gene c-fos. Golgi staining revealed that this treatment also increased spine density in the principal apical dendrite of pyramidal neurons. These results indicate that, apart from the medial prefrontal cortex or the hippocampus, other cortical regions can respond to chronic antidepressant treatment undergoing neuronal structural plasticity.