Deep brain stimulation of Hippocampus in Treatment-resistant Schizophrenia (DBS-HITS): protocol for a crossover randomized controlled trial

• Published in: BMC psychiatry 2024-11, Vol.24 (1), p.847-8, Article 847
• Main Authors: Lu, Chang, Zhai, Zhaolin, Zhuo, Kaiming, Xiang, Qiong, Xue, Jingxin, Zhao, Yuqing, Lang, Liqin, Shao, Chunhong, Chen, Liang, Liu, Dengtang
• Format: Article
• Language: English
• Subjects: Adult; Brain stimulation; Care and treatment; Consent; Cross-Over Studies; Deep brain stimulation; Deep brain stimulation (DBS); Deep Brain Stimulation - methods; Development and progression; Dopamine; Electroencephalography - methods; Female; Functional morphology; General anesthesia; Health aspects; Hippocampus; Hippocampus (Brain); Hippocampus - diagnostic imaging; Hippocampus - physiopathology; Humans; Hyperactivity; Hypotheses; Limbic system; Male; Mental disorders; Mental health; Mesencephalon; Middle Aged; Neuromodulation; Neurosurgery; Patients; Psychosis; Randomized controlled trial (RCT); Schizophrenia; Schizophrenia - physiopathology; Schizophrenia - therapy; Schizophrenia, Treatment-Resistant - therapy; Study Protocol; Surgery; Synchronization; Tomography; Treatment-resistant schizophrenia (TRS); Young Adult; γ-Aminobutyric acid
• ISSN: 1471-244X; 1471-244X
• DOI: 10.1186/s12888-024-06318-6

Ventral hippocampus (vHipp) in schizophrenia is in a state of hyperactivity and hypermetabolism, where the glutamate/gamma-aminobutyric acid (GABA) imbalance leads to downstream dopamine hyperactivity in the midbrain-limbic system. High-frequency deep brain stimulation (DBS) can disrupt the abnormal synchronization of functional circuits and modulate local brain networks. The DBS-HITS study is a crossover randomized controlled trial. DBS will be applied to bilateral vHipp in six patients. They will be randomly assigned to receive 3-month high-frequency active stimulation and then 3-month sham stimulation, or vice versa. After 6-month crossover trial phase, all participants will undergo personalized active stimulation. Researchers will assess clinical symptoms and neurocognition, collect EEG and PET-CT data during planned follow-ups. Adverse event will be researcher-assessed or participant self-reported throughout the trial. To our knowledge, the DBS-HITS study is the first hippocampal DBS randomized controlled trial for schizophrenia. The goal of the DBS-HITS study is to assess the efficacy and safety of hippocampal DBS in treatment-resistant schizophrenia (TRS) and to investigate its impact on hippocampal activity and glutamate/GABA metabolism. The study is expected to deepen our understanding of the effects and side-effects of neuromodulation in TRS to facilitate individualized DBS treatment. NCT05694000 in ClinicalTrial.gov, registered on January 23, 2023.