New Hypothesis on the Pathophysiology of Psychiatric Disorders Illuminates Shared Mechanism of Past and Emergent Treatment Strategies

Abstract

Although psychotherapy and pharmacotherapy continue to be first-line treatments for a wide range of mental and emotional disorders, a high percentage of patients are ultimately considered to be treatment-resistant. For more than half a century, electroconvulsive therapy had been the gold-standard for such patients. However, in recent years a variety of alternative treatment modalities have been developed for these patients, including deep brain stimulation, vagus nerve stimulation, repetitive transcranial magnetic stimulation, stellate ganglion block, and sub-anesthetic doses of the dissociative drug ketamine. Although these alternative treatments have offered new hope for many patients, there is a great deal of individual variability in their degree of effectiveness, and their mechanisms of action, like standard treatments, remain unclear. However, an emerging hypothesis contends that psychiatric symptoms are driven by pathological hyperactivity in symptom-related circuits in the brain. According to the Multi-Circuit Neuronal Hyperexcitability (MCNH) Hypothesis of Psychiatric Disorders, persistent firing in anxiety circuits causes persistent feelings of anxiety; persistent firing in depressive circuits causes persistent feelings of depression; persistent firing in cognitive circuits causes ruminative and obsessive thoughts; etc... The aim of this review is twofold: the first is to discuss the new hypothesis in relation to the aforementioned treatment strategies; and the second is to tease out the shared neurophysiological effects of past and present treatment strategies to determine whether they support or refute the new hypothesis. Clarifying the cause of mental illness is of critical importance to curbing the escalating mental health crisis, as new medications and emergent treatment strategies are failing to keep up with the steady rise in domestic disputes, suicides, homicides, and mass shootings that are driving the disintegration of individuals, families, and communities.