Topics and Speakers Jeremy Coplan, MD
| ||||||
Synopsis
The recent discovery that neurogenesis, the formation of new neurons, occurs in humans has attracted widespread attention both within and without the scientific community. In this lecture, Dr Jeremy Coplan provides an update on current research on neurogenesis. Following the first recognition that neurogenesis occurs in humans, there was great excitement that this phenomenon would have relevance for the neurodegenerative disorders, such as Huntington's and Parkinson's. However, it turns out that neurogenesis offers the most relevance to psychiatric disorders, in particular mood and anxiety disorders. By drawing parallels between current studies and clinical psychopharmacology, Dr Coplan explains what implications neurogenesis research holds for improved treatment of psychiatric disorders.
Postnatal neurogenesis is a much more widespread phenomenon than previously believed, both within the brain and across the life span. Dr Coplan describes studies of terminally ill patients whose brains were studied post mortem; within weeks of death, the patients' brains were generating new neurons. Neurogenesis was previously believed to occur only in the dentate gyrus and subventricular zone of the hippocampus, but recent research has shown that neurogenesis also takes place in the amygdala and the hypothalamus. Since these two areas are involved in emotional regulation and executive function, the finding that new neuronal connections can develop in these brain regions offers hope for the treatment of psychiatric disorders characterized by dysfunction in these areas.
Dr Coplan's principal argument is that factors that inhibit or stimulate neurogenesis are also factors that are highly relevant to the pathogenesis of depression and anxiety disorders, both in terms of etiology but also treatment. Stress, alcohol, sleep deprivation, hypothyroidism and opiates: all are factors that inhibit neurogenesis and also trigger mood disorders. Stress also leads to increased glutamate, an excitatory amino acid that is increasingly implicated in the pathophysiology of anxiety and mood disorders. The converse is also true: factors, such as exercise and antidepressant medication, that improve mood also seem to stimulate neurogenesis. Despite their different mechanisms of action, all antidepressants appear to share the common property of stimulating neurogenesis. Antidepressant treatment may increase extra-hippocampal GABAergic interneurons.
Coplan describes three studies that examine the potential link between neurogenesis and mood disorders. First, he examines a study of electroconvulsive shock therapy on normal primates, which found that administering ECS increased proliferation of precursor cells, a hallmark of neurogenesis. ECS specifically led to increased neurogenesis in the cingulate cortex, a brain region involved in executive function, such as work and social functioning. This finding points to the mechanism by which ECS improves depression.
In the second study, Dr Coplan examines the relationship between stress, neurogenesis, and antidepressants (fluoxetine) in nonhuman primates. When subjected to the stress of repeated social separation, primates exhibit depressive behaviors as well as inhibition of hippocampal neurogenic activity. However, these effects did not occur in stressed primates treated with fluoxetine.
The third study examines the long-term impact of early life stress on nonhuman primate neurogenesis and behavioral depression. Early disruption of maternal-infant attachment leads to persistent and pervasive effects on affective behavior and neurobiological abnormalities related to human anxiety and mood stressors. Neurohistological evidence confirms that early life stress appears to suppress neurogenesis.
The prevalence of mood and anxiety disorders places an enormous health burden on the general population. New and better treatments can only develop with improved understanding of the mechanisms by which these psychiatric disorders develop. Dr Coplan's lecture elegantly summarizes the cutting edge field of research.
