A New Strategy for Antidepressant Prescription

Lavergne, Francis; Jay, Thérèse M.

doi:10.3389/fnins.2010.00192

Cited by 38 publications

(33 citation statements)

References 124 publications

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“…Dopamine signaling is thought to affect consciousness by modulating cortico-basal ganglia-thalamic loops, with a central end mechanism being the impact upon glutamate-GABA processes in frontal cortical and temporal lobe regions (131). Several authors have suggested that dopamine system activation by ECT contributes to reduced depressive and anxious mood and increased positive mood, motivation, concentration, and attention, in line with the general effects of dopamine (133, 134). Within this scenario, frontotemporal effects of HPA axis activation may be closely associated with the dopamine system effects, as indicated for example by the role of glucocorticoid receptors in increasing PFC dopamine efflux following acute stress (135).…”

Section: Discussionmentioning

confidence: 92%

Electroconvulsive Treatment: Hypotheses about Mechanisms of Action

Fosse¹,

Read²

2013

Front. Psychiatry

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No consensus has been reached on the mode of action of electroconvulsive treatment (ECT). We suggest that two features may aid in the delineation of the involved mechanisms. First, when effective, ECT would be likely to affect brain functions that are typically altered in its primary recipient group, people with severe depression. Central among these are the frontal and temporal lobes, the hypothalamus-pituitary-adrenal (HPA) stress axis, and the mesocorticolimbic dopamine system. Second, the involved mechanisms should be affected for a time period that matches the average endurance of clinical effects, which is indicated to be several days to a few weeks. To identify effects upon frontal and temporal lobe functioning we reviewed human studies using EEG, PET, SPECT, and fMRI. Effects upon the HPA axis and the dopamine system were assessed by reviewing both human and animal studies. The EEG studies indicate that ECT decelerates neural activity in the frontal and temporal lobes (increased delta and theta wave activity) for weeks to months. Comparable findings are reported from PET and SPECT studies, with reduced cerebral blood flow (functional deactivation) for weeks to months after treatment. The EEG deceleration and functional deactivation following ECT are statistically associated with reduced depression scores. FMRI studies indicate that ECT flattens the pattern of activation and deactivation that is associated with cognitive task performance and alters cortical functional connectivity in the ultra slow frequency range. A common finding from human and animal studies is that ECT acutely activates both the HPA axis and the dopamine system. In considering this evidence, we hypothesize that ECT affects the brain in a similar manner as severe stress or brain trauma which activates the HPA axis and the dopamine system and may compromise frontotemporal functions.

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Section: Discussionmentioning

confidence: 92%

Electroconvulsive Treatment: Hypotheses about Mechanisms of Action

Fosse¹,

Read²

2013

Front. Psychiatry

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“…It offered a novel perspective on etiology of MDD, but one that fit with the existing “scaffolding”: the concept of MDD as a limbic disorder marked by hippocampus maladaptations. The hypothesis also helped to explain the delay of several weeks between the initiation of antidepressant treatment and onset of their effects (Lavergne and Jay, 2010), since the maturation of the hippocampal progenitors into mature DG granule neurons and their incorporation into circuitry also takes about 3–4 weeks (Encinas et al, 2006; Kee et al, 2007; Kempermann et al, 2004). The tractability of the hypothesis, along with the rapid rate of discovery about neural stem cells, stages of neurogenesis, and novel ways to track, label and manipulate adult-generated neurons (e.g.…”

Section: The Neurogenesis Hypothesis Of Depression: An Overviewmentioning

confidence: 99%

“…This work by Cameron’s group also clarifies how the first postulate should be stated in the future: reduced neurogenesis may result in increased-depressive like behavior when the individual is stressed. However, since the neurobiology of depression relies on many different aspects of brain functioning and involves many proposed cellular and molecular mechanisms including changes in neurotrophic factors, synaptic plasticity, and even cell proliferation and survival outside of hippocampus (Castro et al, 2010; Krishnan and Nestler, 2008; Lavergne and Jay, 2010), it is unlikely that the adult hippocampal neurogenesis would influence them all. Similarly, antidepressants modulate a wide spectrum of brain functions and processes besides adult neurogenesis (Berton et al, 2006).…”

Section: New Scaffolding Needed To Keep Up With Constructionmentioning

confidence: 99%

The neurogenesis hypothesis of affective and anxiety disorders: Are we mistaking the scaffolding for the building?

2012

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Hypotheses are scaffoldings erected in front of a building and then dismantled when the building is finished. They are indispensable for the workman; but you mustn't mistake the scaffolding for the building. Johann Wolfgang von Goethe. The neurogenesis hypothesis of affective disorders – in its simplest form – postulates that the generation of neurons in the postnatal hippocampal dentate gyrus is involved in the etiology and treatment efficacy of major depressive disorder (MDD). The hypothesis was established in the 1990s but was built on a broad foundation of earlier research on the hippocampus, serotonin and MDD. It has gone through several growth phases fueled by discoveries both correlative and causative in nature. Recently, the hypothesis has also been broadened to also include potential relevance for anxiety disorders, like post traumatic stress disorder (PTSD). As any hypothesis should be, it has been tested and challenged, sometimes vigorously. Here we review the current standing of the neurogenesis hypothesis of affective and anxiety disorders, noting in particular how a central postulate – that decreased neurogenesis results in depression or anxiety – has, in general, been rejected. We also review the controversies on whether treatments for these disorders, like antidepressants, rely on intact neurogenesis for their efficacy, and the existence of neurogenesis-dependent and -independent effects of antidepressants. In addition, we review the implications that the hypothesis has for the response to stress, PTSD, and the neurobiology of resilience, and highlight our own work showing that adult-generated neurons are functionally important for the behavioral response to social stress. We conclude by emphasizing how advancements in transgenic mouse technology, rodent behavioral analyses, and our understanding of the neurogenesis process will allow us to refine our conclusions and perform ever more specific experiments. Such scrutiny is critical, since if we “mistake the scaffolding for the building” we could overlook opportunities for translational impact in the clinic.

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“…Depression is a psychiatric disorder that presents as a reduction in self-confidence and a lack of confidence in the world and the future (1). Its core symptoms involve a depressed mood, anhedonia, irritability, difficulties in concentrating and abnormalities in appetite and sleep (2).…”

Section: Introductionmentioning

confidence: 99%

Comparison between the pharmacokinetics of meranzin hydrate in a rat model of chronic depression and in controls following the oral administration of Chaihu-Shugan-San

Xie

Qiu

Huang

et al. 2013

Experimental and Therapeutic Medicine

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Previous studies have shown that meranzin hydrate (MH) may be beneficial in depressive disorders. However, to the best of our knowledge, the pharmacokinetic characteristics of MH in depression have not previously been investigated. Chronic mild stress (CMS) in rats is used as a model of depression. The present study was designed to evaluate and compare the pharmacokinetics of MH in CMS and control rats following the oral administration of Chaihu-Shugan-San (CSS). Rats were randomly divided into CMS and control groups and blood samples were obtained following the oral administration of CSS. The quantification of MH levels in the plasma for pharmacokinetic study was achieved using a simple and rapid ultra-performance liquid chromatography with photodiode array (UPLC-PDA) method. Following the oral administration of CSS to CMS rats and controls, the maximum plasma concentration (Cmax) of MH was 58.66±6.64 and 57.54±12.67 ng/ml at 108.00±26.83 and 54.00±8.22 min, respectively. Compared with the value of the area under the concentration-time curve (AUC)0-1440 in control rats (19,896.76±1,041.95 μg·min/l), the AUC0-1440 value was reduced in CMS rats (18,401.32±4332.65 μg·min/l). There were no significant differences in the majority of the pharmacokinetic parameters of MH, including the values for Cmax, AUC0-1440, clearance rate (CL/F) and mean residence time (MRT0-1440), between the CMS rats and the controls. However, the pharmacokinetic parameters showed that CMS accelerated the absorption of MH in rats following the oral administration of CSS.

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A New Strategy for Antidepressant Prescription

Cited by 38 publications

References 124 publications

Electroconvulsive Treatment: Hypotheses about Mechanisms of Action

Electroconvulsive Treatment: Hypotheses about Mechanisms of Action

The neurogenesis hypothesis of affective and anxiety disorders: Are we mistaking the scaffolding for the building?

Comparison between the pharmacokinetics of meranzin hydrate in a rat model of chronic depression and in controls following the oral administration of Chaihu-Shugan-San

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