Bipolar Disorder Breakthrough
Cause of mania-depression cycling identified After studying individual brain neurons, glial cells, and ion channels for over four years, William J. Walsh, Ph.D., and Robert A. de Vito, M.D., believe they have solved many of the bipolar mysteries that have puzzled researchers for a century, including the causes and mechanisms of bipolar switching between mania and depression. More than six million Americans have been diagnosed with this disorder which continues to be a leading cause of suicide, unemployment, and loss of human potential. |
Dr. Walsh presented their findings at the annual meeting of the American Psychiatric Association (APA) in New York City on May 8, 2018. They found a single mechanism – a lost ability to form proper resting potentials (voltages) in parts of the brain – could cause bipolar disorder. This was a surprise since most experts believe bipolar is a very complex disorder with a multitude of causes and predisposing factors.
The potassium ion gradient across a neuron's membrane determines the magnitude of its rest potential. According to their model, mass transport changes during mania result in excessive buildup of potassium ions outside neurons that eventually disable local brain regions and ushers in depression. Disabled brain sites slowly recover and mania returns due to reduced potassium outflow while clearance mechanisms continue to operate. In absence of effective treatment, a person may be trapped in life-long cycles of mania and depression.
The investigators believe bipolar onset occurs when epigenetic insults trigger sudden and permanent changes in expression of numerous ion-channel genes. Hundreds of genes collaborate to produce rest potentials explaining why a dominant bipolar gene has never been found for this disorder that runs so strongly in families. This theory explains (a) the frequent cases of sudden onset, (b) why the condition does not "go away" after onset, and (c) the important roles of emotional trauma, physical injury, and environmental insults.
Recent advances by dozens of neuroscience and epigenetics researchers were central to these discoveries and development of the new bipolar theory. The improved understanding of bipolar disorder resulting from this study may lead to improved treatments for this devastating disorder.
The potassium ion gradient across a neuron's membrane determines the magnitude of its rest potential. According to their model, mass transport changes during mania result in excessive buildup of potassium ions outside neurons that eventually disable local brain regions and ushers in depression. Disabled brain sites slowly recover and mania returns due to reduced potassium outflow while clearance mechanisms continue to operate. In absence of effective treatment, a person may be trapped in life-long cycles of mania and depression.
The investigators believe bipolar onset occurs when epigenetic insults trigger sudden and permanent changes in expression of numerous ion-channel genes. Hundreds of genes collaborate to produce rest potentials explaining why a dominant bipolar gene has never been found for this disorder that runs so strongly in families. This theory explains (a) the frequent cases of sudden onset, (b) why the condition does not "go away" after onset, and (c) the important roles of emotional trauma, physical injury, and environmental insults.
Recent advances by dozens of neuroscience and epigenetics researchers were central to these discoveries and development of the new bipolar theory. The improved understanding of bipolar disorder resulting from this study may lead to improved treatments for this devastating disorder.
A Neuroscience Theory of Bipolar
William J. Walsh, PhD, FACN, and Robert A. deVito, MD |