Topics and Speakers René Hen, PhD
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Synopsis
Depressive disorders are both highly prevalent and highly fatal. The chance that an individual will be afflicted over the course of a lifetime is 10% and in any given year about 10% of patients with depression attempt suicide. In this lecture, Dr René Hen reviews the pathological hallmarks of mood and anxiety disorders, their symptoms, treatments and current understanding about their neurobiological underpinnings.
As Dr Hen points out, linking mood and anxiety disorders together is not arbitrary. With comorbidity between 30% and 60%, mood and anxiety disorders rarely exist independently of each other. In addition, the same drugs can effectively treat both families of disorders, suggesting certain commonalities in the circuits and pathways.
There are two broad categories of depression: bipolar disorder, characterized by alternations between a depressed and a manic phase, and the depressive disorders, which are further subdivided into other categories. Treatment for depression includes medication, psychotherapy, and electroconvulsive therapy. One of the paradoxes of pharmacological antidepressants is that there is a fast onset of neurochemical changes but slow onset of therapeutic benefits. In addition, a significant fraction of people do not respond to these medications. Electroconvulsive therapy has the advantage of working faster than antidepressants but has many side effects, including loss of memory.
Anxiety disorders include generalized anxiety disorder, panic disorder, phobias and posttraumatic stress disorder. Dr Hen reviews the hallmarks and triggers for each. A difficult disorder to categorize is obsessive-compulsive disorder, which is sometimes characterized as an anxiety disorder and sometimes not. It eludes easy classification because while the obsession component involves anxiety, the compulsive component is usually a motor act that involves different brain pathways. The most commonly prescribed medication for anxiety are the benzodiazepines, which work well but only have a short-lasting effect and can cause side effects such as sedation and dependence.
As Dr Hen points out, in diagnosing mood and anxiety disorders, it is critical to remember that these disorders exist on a spectrum between normal and pathological response. Unlike in other medical categories where there is a clear line between healthy and sick, the division between normal and pathological mood is more nebulous.
Genes and environment act in concert to influence how brain substrates develop and function. During childhood, the developing brain is particularly vulnerable to both environmental and genetic insults. An individual's vulnerability to mood or anxiety disorders varies depending on the alleles in the cells and the environment he or she encounters. Dr Hen illustrates gene-environment interactions further by describing how both factors modulates serotonin transporters.
Dr Hen describes the specific circuits in the brain that mediate the fear response; pathologies in these fear-mediating circuits can contribute to anxiety and depressive disorders. Several studies have shown an association between prolonged stress (such as combat) and reduced volume in the hippocampus. However, whether that shrinkage is a cause or a consequence of the severe stress remains to be determined.
Antidepressants include not only pharmacological treatments, such as SSRIs, but also somatic ones, such as electroconvulsive therapy, and environmental conditions, such as exercise. All types of antidepressants have been found to increase neurogenesis. This finding has lead to the current hypothesis that antidepressants may work by increasing neurogenesis, thereby reversing the dendritic shrinkage caused by depression. As Dr Hen concludes, future research will aim at developing novel antidepressants that target neurogenesis.
