Using Low-Intensity Focused Ultrasound to Treat Depression and Anxiety Disorders: A Review of Current Evidence

Background: Depression and anxiety disorders impact millions globally. In recent years, low-intensity focused ultrasound (LIFU), characterized by its high precision, deep penetration, and non-invasive nature, has garnered significant interest in neuroscience and clinical practice. To enhance understanding of its effects on mood, therapeutic availability in treatment of depression/anxiety disorders, and potential mechanisms, a systematic review of studies investigating the emotional impact of LIFU on depressive/anxious-like animal models, healthy volunteers, and patients with depression or anxiety disorders has been undertaken. Methods: Relevant papers published before 15 July 2025 were searched across four databases: Web of Science, PubMed, Science Direct, and Embase. A total of 28 papers which met the inclusion and exclusion criteria are included in this review. Results: Our findings indicate that LIFU reversed the depressive/anxious-like behaviors in the animal models and showed antidepressant/anti-anxiety effects among the state-of-art clinical studies. For example, immobility time in FST or TST is reduced in depressive animal models, and HRSD/BAI scales are improved in human studies. Key molecules such as BDNF/5-HT are found restored in animal models, and FC between key brain areas related to depression/anxiety is modulated after LIFU treatment. Notably, no brain tissue damage was observed in animal studies, and only mild adverse effects (such as dizziness and vomiting) were noted in a few human studies. Conclusions: The studies using LIFU to treat depression and anxiety remain in the preliminary stage. The mechanisms underlying LIFU's mood effects-such as activation or inhibition of specific brain regions or neural circuits, anti-inflammatory effects, alterations in functional connectivity, synaptic plasticity, neurotransmitter levels, and BDNF-remain incompletely understood and warrant further investigation. Nevertheless, the LIFU technique holds promise for regulating both cortical and subcortical brain areas implicated in depression/anxiety disorders as a precise neuromodulation tool.