For treatment-resistant mood disorders, intensive interventions such as electroconvulsive therapy, transcranial magnetic stimulation, ketamine, and esketamine are commonly used, but how genetics influences response to these therapies remains unclear. A review of the current literature finds that most studies have examined single variants in candidate genes, particularly COMT and BDNF, yet none have been consistently reproducible. Genome-wide association studies are few and mostly underpowered, with only one exceeding 1000 participants, yielding few statistically significant single nucleotide polymorphisms outside COMT and BDNF. Large-scale data collection is needed to establish genetic predictors and differentiate responses among treatments, a goal being pursued by the worldwide Gen-ECT-ic consortium.
Social deficits in schizophrenia may stem from underactivity in a specific brain region called the lateral septum (LS). In mice given chronic ketamine to model schizophrenia-like symptoms, the LS showed reduced activation during social encounters. Artificially stimulating the LS restored normal social behavior, while silencing it in healthy mice caused social impairments. Genetic analysis of LS neurons revealed dysregulation of genes linked to neuronal excitability and cell death, with 38 genes overlapping those implicated in human schizophrenia. Activating LS neurons triggered activity in brain areas involved in reward, fear, and sensory processing. The findings suggest the LS acts as a central hub for social behavior, and its dysfunction may underlie social challenges in schizophrenia, pointing to potential targets for new therapies.