Successful Electroconvulsive Therapy in a Patient With Catatonia and Maternal Duplication 15q11-13 Syndrome.

ABSTRACT: The 15q11-q13 chromosomal region contains genes encoding for GABA-A receptor subunits and is a known region of epigenetic modification associated with the development of neurodevelopmental disorders. The presence of at least one additional copy of the maternal 15q11-q13 results in a syndrome (maternal dup15q) characterized by intellectual disability, autism spectrum disorder, mood disorders, and epilepsy. Catatonia is a serious syndrome of behavioral and motor dysfunction, which occurs across a variety of psychiatric, neurologic, and general medical conditions, which has successfully been treated with benzodiazepines and electroconvulsive therapy. In this case report, we describe the treatment course of a patient with established maternal dup 15q with comorbid intellectual disability, autism spectrum disorder, bipolar mood disorder, and juvenile epilepsy who developed hypokinetic catatonia refractory to high-dose benzodiazepine therapy. In contrast with benzodiazepine treatment, electroconvulsive therapy resulted in rapid improvement in catatonic symptoms and return to premorbid baseline. This case suggests that electroconvulsive therapy can be safely delivered for some patients with maternal dup 15q and may be rapidly effective when benzodiazepine treatment results in inadequate symptom improvement.

BK channel deacetylation by SIRT1 in dentate gyrus regulates anxiety and response to stress.

Previous genomic studies in humans indicate that SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, is involved in anxiety and depression, but the mechanisms are unclear. We previously showed that SIRT1 is highly activated in the nuclear fraction of the dentate gyrus of the chronically stressed animals and inhibits memory formation and increases anhedonic behavior during chronic stress, but specific functional targets of cytoplasmic SIRT1 are unknown. Here, we demonstrate that SIRT1 activity rapidly modulates intrinsic and synaptic properties of the dentate gyrus granule cells and anxiety behaviors through deacetylation of BK channel α subunits in control animals. Chronic stress decreases BKα channel membrane expression, and SIRT1 activity has no rapid effects on synaptic transmission or intrinsic properties in the chronically stressed animal. These results suggest SIRT1 activity rapidly modulates the physiological function of the dentate gyrus, and this modulation participates in the maladaptive stress response.