Hippocampal Angiogenesis and Progenitor Cell Proliferation Are Increased with Antidepressant Use in Major Depression

Boldrini, Maura; Hen, René; Underwood, Mark D.; Rosoklija, Gorazd; Dwork, Andrew J.; Mann, J. John; Arango, Victoria

doi:10.1016/j.biopsych.2012.04.024

Cited by 284 publications

(264 citation statements)

References 97 publications

(139 reference statements)

Supporting

Mentioning

236

Contrasting

Order By: Relevance

“…Nevertheless, this was the hallmark study which provided valuable data for human in vivo neurogenesis in depressive disease conditions. In contrast to this study, two recently published studies showed that antidepressant treatment in major depression patients increased the number of neural precursor cells and angiogenesis in the mid and anterior dentate gyrus [27]. The discrepancy between the two studies may be due to the use of different immunochemical markers and quantification methods, which should be verified in future studies.…”

Section: Neurogenesis and Depressive Disordercontrasting

confidence: 75%

Neurogenic hypothesis and psychiatric disorders

Lau

Lee

2013

Chin. Sci. Bull.

View full text Add to dashboard Cite

Psychiatric illness, such as affective disorders, anxiety disorders and schizophrenia, exerts exceptional personal burden on affected individuals. Although not physically noticeable, these disorders cost enormously on ones' family and society. Currently pharmaceutical and psychological treatments are generally accepted as effective for psychiatric disorders, while the exact mechanisms underlying the treatment efficacy, etiology and neurobiology of the disorders remain elusive. In the past decade, "neurogenic hypothesis" emerged as an attempt to explain the nature of psychiatric illness. The origination of the hypothesis is based on several pre-clinical and clinical observations. First, stress, which is a common risk factor of the disorders, was found to suppress neurogenesis; second, treatment for the illnesses like antidepressants and antipsychotics were shown to improve neurogenesis and behavioral deficits simultaneously; and third, the therapeutic effect of antidepressants was abolished in animal models when neurogenesis was blocked. Increasing efforts were invested to determine whether neurogenesis is a key to the understanding and treatment of psychiatric disorders, although contrasting results are also found and thus the importance of neurogenesis remains a matter of debate. The present chapter will discuss the recent findings about the involvement of neurogenesis in major depression, anxiety disorders and schizophrenia, and whether neurogenesis would be a potential target for development of the treatment in the future.neurogenesis, psychiatric disorders, major depression, schizophrenia, anxiety disorder, hippocampus, amygdala, subventricular zone Citation:

show abstract

Section: Neurogenesis and Depressive Disordercontrasting

confidence: 75%

Neurogenic hypothesis and psychiatric disorders

Lau

Lee

2013

Chin. Sci. Bull.

View full text Add to dashboard Cite

show abstract

“…Determinants of hippocampal volume in MDD are not known. Like others (Reif et al, 2006), we did not detect fewer mitotic cells (Boldrini et al, 2009) or neural progenitor cells (NPCs) in the DG postmortem (Boldrini et al, 2009(Boldrini et al, , 2012 in untreated MDD subjects (o58-60 y old) compared to those with no major psychopathology. Notably, blocking (Santarelli et al, 2003) or blunting (Vollmayr et al, 2003) hippocampal proliferation in adulthood is not sufficient to induce depression-like behavior in mice.…”

Section: Introductionmentioning

confidence: 85%

“…The role of the anterior hippocampus (Sahay and Hen, 2007) in emotion regulation would be tied more closely to neurogenesis if effects on neurogenesis were confined to anterior DG. We found that antidepressant-treated MDDs have more mitotic cells and NPCs selectively in the anterior DG (Boldrini et al, 2009(Boldrini et al, , 2012. Therefore, we hypothesized that changes in GN number associated with MDD or antidepressant treatment will be localized to the anterior DG.…”

Section: Introductionmentioning

confidence: 96%

“…Selected brain areas were used for neuropathology, and cerebellar tissue for brain pH and toxicology (see Boldrini et al, 2012 for details). All cases and the control group underwent psychological autopsy, as described elsewhere (Boldrini et al, 2012;Kelly and Mann, 1996).…”

Section: Brain Collectionmentioning

confidence: 99%

“…We compared GN number in the DG of antidepressant-treated and untreated MDD subjects (MDDs), with subjects with no major psychopathology (control group) (Boldrini et al, 2009(Boldrini et al, , 2012. We further compared GN number and DG volume between MDDs treated with serotonin reuptake inhibitors (MDD*SSRI) and tricyclics (MDD*TCA), because SSRIs are serotonergic, and TCAs affect both serotonin and norepinephrine reuptake.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hippocampal Granule Neuron Number and Dentate Gyrus Volume in Antidepressant-Treated and Untreated Major Depression

Boldrini

Santiago

Hen

et al. 2013

Neuropsychopharmacol

Self Cite

293

210

View full text Add to dashboard Cite

Smaller hippocampal volume is reported in major depressive disorder (MDD). We hypothesize that it may be related to fewer granule neurons (GN) in the dentate gyrus (DG), a defect possibly reversible with antidepressants. We studied age-, sex-, and postmortem interval-matched groups: no major psychopathology (controls); unmedicated-MDD; and MDD treated with serotonin reuptake inhibitors (MDD*SSRI) or tricyclics (MDD*TCA). Frozen right hippocampi were fixed, sectioned (50 mm), immunostained with neuronal nuclear marker (NeuN), and counterstained with hematoxylin. GN and glial number, and DG and granule cell layer (GCL) volumes were stereologically estimated. Fewer GNs in the anterior DG were present in unmedicated-MDDs compared with controls (p ¼ 0.013). Younger age of MDD onset correlated with fewer GNs (p ¼ 0.021). Unmedicated-MDDs had fewer mid-DG GNs than MDD*SSRIs (p ¼ 0.028) and controls (p ¼ 0.032). Anterior GCL glial number did not differ between groups. Anterior/mid GCL volume was smaller in unmedicated-MDDs vs controls (p ¼ 0.008) and larger in MDD*SSRIs vs unmedicated-MDDs (po0.001), MDD*TCAs (po0.001), and controls (po0.001). Anterior GCL volume and GN number (r ¼ 0.594, p ¼ 0.001), and mid DG volume and GN number (r ¼ 0.398, p ¼ 0.044) were correlated. Anterior DG capillary density correlated with GN number (p ¼ 0.027), and with GCL (p ¼ 0.024) and DG (r ¼ 0.400, p ¼ 0.047) volumes. Posterior DG volume and GN number did not differ between groups. Fewer GNs in unmedicated-MDD without fewer neuronal progenitor cells, as previously reported, suggests a cell maturation or survival defect, perhaps related to MDD duration. This may contribute to a smaller hippocampus and is potentially reversed by SSRIs. Postmortem studies are correlative and animal studies are needed to test implied causal relationships.

show abstract