The symptoms of emotional dysregulation associated with the syndrome known as pseudobulbar affect (PBA) can be effectively treated by the sigma, glutamate, and serotonergic agent dextromethorphan combined with quinidine. If the same brain circuits affected in PBA are also compromised in related disorders of emotional expression, dextromethorphan-quinidine and other novel sigma-glutamateserotonin agents could prove to be novel psychopharmacologic treatments for these conditions as well.
Take-Home Points' Preoccupation with naming the condition of pathological laughing and crying can obscure the underlying pathophysiology and mechanism of effective psychopharmacological treatment of the syndrome many now call pseudobulbar affect (PBA).' No matter what it is called, the syndrome of PBA with pathological laughing and crying can result when any number of neurological disorders structurally disrupts cortical and/or cerebellar inputs to nerve centers that control emotional expression in the brainstem.' Hypothetically, functional disruption of these same brain cortical/cerebellar brain circuits may underlie not only pathological laughing and crying but also several other labile, unstable, and dysfunctional symptoms of emotional dysregulation in psychiatric disorders, such as behavioral symptoms of dementia, traumatic brain injury, post-traumatic stress disorder, borderline personality disorder, treatment refractory mood disorders, multiple impulsive-compulsive disorders, and beyond.' The observation that dextromethorphan-quinidine reduces the involuntary symptoms of PBA has stimulated the hypothesis that sigma-glutamate-serotonin modulation of brain circuits that regulate emotional expression could provide a novel therapeutic approach to improving symptoms in wide-ranging psychiatric disorders and their symptoms of emotional expression, just as they do in PBA.