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  • Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults NATURE Sorrells, S. F., Paredes, M. F., Ebrian-Silla, A. C., Sandoval, K., Qi, D., Kelley, K. W., James, D., Mayer, S., Chang, J., Auguste, K. I., Hang, E. C., Gutierrez, A. J., Kriegstein, A. R., Mathern, G. W., Oldham, M. C., Huang, E. J., Manuel Garcia-Verdugo, J., Yang, Z., Alvarez-Buylla, A. 2018; 555 (7696): 377-+

    Abstract

    New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n?=?17 post-mortem samples from controls; n?=?12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved.

    View details for DOI 10.1038/nature25975

    View details for Web of Science ID 000427477100038

    View details for PubMedID 29513649

    View details for PubMedCentralID PMC6179355

  • Extensive migration of young neurons into the infant human frontal lobe SCIENCE Paredes, M. F., James, D., Gil-Perotin, S., Kim, H., Cotter, J. A., Ng, C., Sandoval, K., Rowitch, D. H., Xu, D., McQuillen, P. S., Garcia-Verdugo, J., Huang, E. J., Alvarez-Buylla, A. 2016; 354 (6308)
  • Patient-reported functioning in major depressive disorder THERAPEUTIC ADVANCES IN CHRONIC DISEASE IsHak, W., James, D. M., Mirocha, J., Youssef, H., Tobia, G., Pi, S., Collison, K. L., Cohen, R. M. 2016; 7 (3): 160?69

    Abstract

    Compared with the general population, patients with major depressive disorder (MDD) report substantial deficits in their functioning that often go beyond the clinical resolution of depressive symptoms. This study examines the impact of MDD and its treatment on functioning.From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2280 adult outpatients with MDD at entry and exit points of each level of antidepressant treatment and again 12 months post treatment. Functioning was measured using the Work and Social Adjustment Scale (WSAS).The results show that only 7% of patients with MDD reported within-normal functioning before treatment. The proportion of patients achieving within-normal functioning (WSAS) scores significantly increased after treatment. However, the majority of patients (>60%) were still in the abnormal range on functioning at exit. Although remitted patients had greater improvements compared with nonremitters, a moderate proportion of remitted patients continued to experience ongoing deficits in functioning after treatment (20-40%). Follow-up data show that the proportions of patients experiencing normal scores for functioning after 12 months significantly decreased from the end of treatment to the follow-up phase, from 60.1% to 49% (p < 0.0001), a finding that was particularly significant in nonremitters. Limitations of this study include the reliance on self-report of functioning and the lack of information on patients who dropped out.This study points to the importance of functional outcomes of MDD treatment as well as the need to develop personalized interventions to improve functioning in MDD.

    View details for DOI 10.1177/2040622316639769

    View details for Web of Science ID 000376684100003

    View details for PubMedID 27347363

    View details for PubMedCentralID PMC4907070

  • Quality of life in major depressive disorder before/after multiple steps of treatment and one-year follow-up ACTA PSYCHIATRICA SCANDINAVICA IsHak, W. W., Mirocha, J., James, D., Tobia, G., Vilhauer, J., Fakhry, H., Pi, S., Hanson, E., Nashawati, R., Peselow, E. D., Cohen, R. M. 2015; 131 (1): 51?60

    Abstract

    This study examines the impact of major depressive disorder (MDD) and its treatment on quality of life (QOL).From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2280 adult MDD out-patients at entry/exit of each level of antidepressant treatments and after 12 months of entry to follow-up. QOL was measured using the QOL Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The proportions of patients scoring 'within-normal' QOL (within 10% of Q-LES-Q community norms) and those with 'severely impaired' QOL (>2 SD below Q-LES-Q community norms) were analyzed.Before treatment, no more than 3% of MDD patients experienced 'within-normal' QOL. Following treatment, statistically significant improvements were detected; however, the proportion of patients achieving 'within-normal' QOL did not exceed 30%, with >50% of patients experiencing 'severely impaired' QOL. Although remitted patients had greater improvements compared with non-remitters, 32-60% continued to experience reduced QOL. 12-month follow-up data revealed that the proportion of patients experiencing 'within-normal' QOL show a statistically significant decrease in non-remitters.Symptom-focused treatments of MDD may leave a misleading impression that patients have recovered when, in fact, they may be experiencing ongoing QOL deficits. These findings point to the need for investigating specific interventions to ameliorate QOL in MDD.

    View details for DOI 10.1111/acps.12301

    View details for Web of Science ID 000346337700015

    View details for PubMedID 24954156

    View details for PubMedCentralID PMC4267902

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