Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders

Neuronal plasticity and antidepressant actions

S.02.02 - Adult hippocampal neurogenesis and cognitive flexibility - linking memory and mood

Event Abstract Back to Event Functional role of adult-born neurons in memory processes Muriel Koehl1* 1 INSERM U862, Institut Francois Magendie, France The dentate gyrus of the mammalian hippocampus, a region highly involved in spatial memory, is also one of the few regions of the adult brain where new neurons are continuously generated. Although this adult neurogenesis has been proposed to contribute to spatial memory, data showing a causal relationship between neurogenesis and memory performances are controversial. To analyze the contribution of neurogenesis to memory processes, we developed an inducible transgenic strategy allowing specific ablation of adult-born hippocampal neurons. This resulted in an impairment of spatial relational memory, which supports a capacity for flexible, inferential memory expression. In contrast, less complex forms of spatial knowledge were unaltered. Furthermore, transgenic mice displayed specific impairments in a task of pattern separation, a process that transforms similar memories into non-overlapping representations. Altogether, these findings demonstrate that adult-born neurons are necessary for complex forms of hippocampus-mediated learning. Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Topic: Symposium 23 – Adult-born hippocampal neurons and memory Citation: Koehl M (2009). Functional role of adult-born neurons in memory processes. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.087 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Nov 2009; Published Online: 20 Nov 2009. * Correspondence: Muriel Koehl, INSERM U862, Institut Francois Magendie, Bordeaux, France, muriel.koehl@inserm.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Muriel Koehl Google Muriel Koehl Google Scholar Muriel Koehl PubMed Muriel Koehl Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Adult neurogenesis occurs in the hippocampus of most mammals, including humans, and plays an important role in hippocampal-dependent learning. This process is highly regulated by neuronal activity and might therefore be vulnerable to anesthesia. In this article, the authors investigated this possibility by evaluating the impact of propofol anesthesia on mouse hippocampal neurons generated during adulthood, at two functionally distinct maturational stages of their development. Adult-born hippocampal neurons were identified using the cell proliferation marker bromodeoxyuridine or a retroviral vector expressing the green fluorescent protein in dividing cells and their progenies. Eleven or 17 days after the labeling procedure, animals (n = 3-5 animals per group) underwent a 6-h-long propofol anesthesia. Twenty-one days after labeling, the authors analyzed the survival, differentiation, and morphologic maturation of adult-born neurons using confocal microscopy. Propofol impaired the survival and maturation of adult-born neurons in an age-dependent manner. Anesthesia induced a significant decrease in the survival of neurons that were 17 days old at the time of anesthesia, but not of neurons that were 11 days old. Similarly, propofol anesthesia significantly reduced the dendritic maturation of neurons generated 17 days before anesthesia, without interfering with the maturation of neurons generated 11 days before anesthesia. These results reveal that propofol impairs the survival and maturation of adult-born hippocampal neurons in a developmental stage-dependent manner in mice.

Panic disorder has an elevated prevalence in Parkinson's disease (PD). To explore the basis for this co-occurrence, the familial aggregation of panic disorder was examined in patients with PD. Probands and relatives of patients with PD and panic disorder (PD-PANIC; N=20, N=115) and control probands with PD and no active psychiatric illness (PD-NA; N=17, N=108) were interviewed by phone, using a structured interview to determine panic status. Lifetime prevalence of panic and “panic-like” disorders was higher in PD-PANIC than in PD-NA relatives. Panic and “panic-like” disorders are familial disorders in PD.

Diagnosis and Treatment of Depression and Anxiety in Rural and Nonrural Primary Care: National Survey Results

There is growing recognition that the dentate gyrus (DG) subregion of the hippocampus contributes to both cognition and regulation of mood. Because adult hippocampal neurogenesis provides a source of new neurons throughout life in mammals, it represents a unique form of neural plasticity that may be targeted to restore or rejuvenate DG functions when compromised, such as in different disease states and during normal ageing. In this review, we address whether the role of adult-born neurons in modulation of anxiety and depression-like behaviors is dependent on their proposed function in pattern separation. Towards this goal, we discuss evidence for adult-born neurons in pattern separation and mood regulation. We suggest that the functions of adult-born neurons in pattern separation may be particularly relevant for anxiety disorders, such as posttraumatic stress disorder (PTSD), and that antidepressants may engage both pattern separation-dependent and pattern separation-independent functions of adult-born neurons to produce therapeutic effects.

Adult hippocampal neurogenesis (AHN) has intrigued neuroscientists for decades. Several lines of evidence show that adult-born neurons in the hippocampus are functionally integrated and contribute to cognitive function, in particular learning and memory processes. Biological properties of immature hippocampal neurons indicate that these cells are more easily excitable compared with mature neurons, and demonstrate enhanced structural plasticity. The structure in which adult-born hippocampal neurons are situated-the dentate gyrus-is thought to contribute to hippocampus function by disambiguating similar input patterns, a process referred to as pattern separation. Several ideas about AHN function have been put forward; currently there is good evidence in favor of a role for AHN in pattern separation. This function of AHN may be understood within a 'representational-hierarchical' view of brain organization. WIREs Cogn Sci 2014, 5:573-587. doi: 10.1002/wcs.1304 For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article.

The last three decades have witnessed significant advances in psychotherapy. Numerous scholarly articles and books have been devoted to pertinent topics in the field, making it difficult for the practicing clinician to keep up with this rapidly growing area. The purpose of this article is to provide some guidelines on how to evaluate the empirical literature in psychotherapy and then to explore three key areas: evidence-based psychotherapies for patients with psychiatric disorders, individual variables that predict differential outcome to treatment, and the therapeutic alliance. Finally, two case examples will be presented to illustrate how knowledge of the empirical literature can facilitate an evidence-based approach to the daily practice of psychotherapy in general psychiatry.

This review provides an integrative overview of the functional roles of adult neurogenesis in the hippocampal dentate gyrus (DG), focusing specifically on its impact on memory processes across the lifespan. A distinguishing feature of this review is its systematic approach, organizing the contributions of adult-born neurons (ABNs) chronologically through the stages of memory—from initial encoding, through sleep-dependent consolidation, retrieval, and finally forgetting.Although the existence and extent of adult neurogenesis in the human DG remain debated, accumulating evidence suggests that ABNs support cognitive functions throughout adulthood. This perspective gains particular importance when considering cognitive decline associated with aging and neurological disorders such as Alzheimer’s disease, which are linked to substantial reductions in adult neurogenesis.We compare traditional models of DG function with emerging evidence highlighting both shared and unique contributions of ABNs. For example, the DG is well-established for its role in pattern separation, and as key mediators of this function, ABNs—due to their transiently heightened plasticity and excitability—appear critical for discriminating novel or similar experiences. On the other hand, recent findings underscore the distinct and essential role of ABNs in memory consolidation during REM sleep, suggesting specialized functions of ABNs that are absent in developmentally born granule cells in the DG.Clinically, the potential therapeutic importance of enhancing neurogenesis in memory-related disorders, including post-traumatic stress disorder (PTSD), is emphasized, highlighting promising treatments such as memantine. Lastly, we outline key unresolved questions, advocating for future research aimed at understanding ABN-specific mechanisms. Far from being a mere evolutionary vestige, hippocampal ABNs represent dynamic and essential elements of neural plasticity that are critical for memory formation, adaptation, and resilience across the lifespan.

Gabapentin and Pregabalin for the Treatment of Anxiety Disorders.

Aim: Aging and early Alzheimer’s disease (AD) affect pattern separation (PS) based mnemonic discrimination in humans. PS function involves the dentate gyrus (DG), a brain region producing new neurons during adulthood. Aging and AD presumably affect PS and DG function through different mechanisms, although it has never been clearly shown within the same study. Passive immunotherapy targeting β-amyloid peptides (Aβ) was used to determine the relative contribution of abnormal levels of Aβ to early PS deficits in two mouse models of aging and amyloid pathology, and potential involvement of adult neurogenesis. Methods: Female Tg2576 mice were tested in a spatial PS task from the age of three months to determine the age of onset of PS deficits. A cohort of five-month-old female Tg2576 mice and a cohort of 20-month-old male C57BL/6J mice were treated with passive immunization for four weeks, and then tested for PS performance. ELISA assays were used to quantify Aβ levels in CA3/DG regions of these mouse models. DG recruitment during PS testing was assessed with an Egr-1 ex vivo imagery. The contribution of adult-born neurons to a potential rescue of PS performances was evaluated using bromodeoxyuridine and doublecortin co-immunostainings. Results: Spatial PS deficits appeared first in four-month-old female Tg2576 mice, an early pre-plaque stage of Alzheimer pathology. Aβ immunotherapy restored PS performance in Tg2576 mice, but not in aged male C57BL/6J mice. PS impairments were associated with an overactivation of the DG in both models and a potentially abnormal level of immature adult-born neurons in Tg2576 mice. Conclusions: Alleviation of PS deficits following Aβ immunotherapy in Tg2576 mice is associated with reduced DG activation and improved adult-born neurons maturation. The absence of beneficial effects in aged mice suggests that PS deficits in aging and AD may be related to different underlying mechanisms.

This article reviews the current screening and assessment tools for anxiety disorders in children and adolescents, as well as evidence-based treatment interventions for these disorders. The following anxiety disorders are discussed: separation anxiety disorder, generalized anxiety disorder, specific phobia, panic disorder, social anxiety disorder (social phobia), and selective mutism. There are several well-studied screening and assessment tools to identify childhood anxiety disorders early and differentiate the various anxiety disorders. Evaluations of baseline somatic symptoms, severity, and impairment ratings of the anxiety disorders, and collecting ratings from several sources is clinically helpful in assessment and treatment follow-up. Cognitive-behavioral therapy (CBT) has been extensively studied and has shown good efficacy in treatment of childhood anxiety disorders. A combination of CBT and medication may be required for moderate to severely impairing anxiety disorders and may improve functioning better than either intervention alone. Selective serotonin reuptake inhibitors are currently the only medications that have consistently shown efficacy in treatment of anxiety disorders in children and adolescents. Despite proven efficacy, the availability of CBT in the community is limited. Current research is focusing on early identification of anxiety disorders in community settings, increasing the availability of evidence-based interventions, and modification of interventions for specific populations.

Anxiety disorders are the most common mental health disorders. While the older tricylic antidepressants (TCAs) are efficacious in the treatment of many anxiety disorders, recent studies with fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) have emphasized the role of serotonin in the aetiology of these conditions. We reviewed the efficacy, safety and tolerability of TCAs and SSRIs in the treatment of the most common anxiety disorders, specifically, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, social phobia and generalized anxiety disorder. Both the TCA and SSRI antidepressants are effective in treating a wide variety of anxiety disorders. SSRIs, due to their greater safety and tolerability, should be the preferred choices in treating anxiety disorders in those instances where TCAs and SSRIs are considered equally effective. In the cases of OCD and social phobia, SSRIs are almost always preferable given that the TCAs do not appear effective in these disorders. Further research is needed on the naturalistic long-term use of the TCAs and SSRIs in the treatment of anxiety disorders.

RGS6 Mediates Effects of Voluntary Running on Adult Hippocampal Neurogenesis