Cognitive Role of Neurogenesis in Depression and Antidepressant Treatment

Abstract

The discovery of newborn neurons in the adult brain has generated enormous interest over the past decade. Although this process is well documented in the hippocampus and olfactory bulb, the possibility of neuron formation in other brain regions is under vigorous debate. Neurogenesis within the adult hippocampus is suppressed by factors that predispose to major depression and stimulated by antidepressant interventions. This pattern has generated the hypothesis that impaired neurogenesis is pathoetiological in depression and stimulation of newborn neurons essential for effective antidepressant action. This review critically evaluates the evidence in support of and in conflict with this theory. The literature is divided into three areas: neuronal maturation, factors that influence neurogenesis rates, and function of newborn neurons. Unique elements in each of these areas allow for the refinement of the hypothesis. Newborn hippocampal neurons appear to be necessary for detecting subtle environmental changes and coupling emotions to external context. Thus speculatively, stress-induced suppression of neurogenesis would uncouple emotions from external context leading to a negative mood state. Persistence of negative mood beyond the duration of the initial stressor can be defined as major depression. Antidepressant-induced neurogenesis therefore would restore coupling of mood with environment, leading to the resolution of depression. This conceptual framework is provisional and merits evaluation in further experimentation. Critically, manipulation of newborn hippocampal neurons may offer a portal of entry for more effective antidepressant treatment strategies.

Potential for Transcranial Laser or LED Therapy to Treat Stroke, Traumatic Brain Injury, and Neurodegenerative Disease

“…Light therapy for Parkinson's disease (PD) has been studied in an in vitro model of PD human transmitochondrial cybrid ''cytoplastic hybrid'' neuronal cells, 39 and in a clinical study of 70 patients in Russia. 40 The realization that impaired neurogenesis plays an important role in depression 41 suggested that TLT could have beneficial effects in patients with major depression and anxiety, and this was confirmed in a pilot clinical trial with 10 subjects receiving a single TLT to the forehead. 36 TLT may be thought to be just in its infancy, but we believe the stage is set for rapid growth, especially in view of the massive and continuing failure of clinical trials of pharmaceuticals for many brain disorders.…”

Adult Neurogenesis and Psychiatric Disorders

“…Since the original proposal, numerous studies have either argued in favor of or against the hypothesis, which has evolved to postulate that decreased generation of new neurons in the hippocampus contributes to the pathogenesis of depression, and enhancing adult hippocampal neurogenesis is necessary for successful antidepressant treatments (Duman 2004;Sahay and Hen 2007). This hypothesis is supported by the finding that antidepressants stimulate production of newborn neurons in the adult brain, which can partially repair structural abnormalities in the hippocampus of depressed patients (Sheline et al 2003;Bremner and Vermetten 2004;Perera et al 2008). Similarly, promoting adult hippocampal neurogenesis is sufficient to mimic antidepressant action (Santarelli et al 2003;Reif et al 2007;Sahay and Hen 2007).…”

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

“…Newly generated neurons in the adult mouse hippocampus may be integrated into the dentate granule cell circuitry and can display functional properties similar to those found in mature dentate granule cells (90). Thus, neurogenesis plays a crucial role in behavioral, physiological and cognitive processes (91,92), and much attention has been focused on hippocampal neurogenesis in relation to the pathophysiology and treatment of depression (93,94). Jin et al (95) investigated the effect of galantamine on neurogenesis, measured by labeling newborn cells with bromodeoxyuridine (BrdU), in mouse cerebral cortical cultures in vitro and in the SGZ and SVZ of mice in vivo.…”