Recent advances and perspectives of small molecule fluorescent probes imaging in depression research

Depression is one of the most disabling mental illnesses in the world, and it has a high incidence of morbidity. The etiology of depression is intricate and involves abnormal changes in a variety of biologically active substances, such as neurotransmitters, reactive oxygen species, biothiols, gas signaling molecules, and metal ions. Deepening the comprehension of these substances' roles in depressive disorders is critically important for improving disease diagnosis and treatment strategies. In recent years, small molecule probe imaging technology has shown great potential in the early diagnosis of depression, monitoring of the disease process, evaluation of treatment response, and development of new drugs. This review details depression-related biomarkers and their roles in the disease, focusing on the design principles, recognition mechanisms, and imaging applications of small molecule probes in depression models. The current challenges of small molecule probes imaging in depression research, such as blood-brain barrier (BBB) penetration, specific biomarker identification, signaling pathway assessment, targeting strategy enhancement, multimodal imaging with imaging depth enhancement, and multi-biomarker probe development, are also discussed. Finally, the future direction of small molecule imaging probe technology in depression research is envisioned, and suggestions such as improving probe BBB penetration and reducing cytotoxicity are proposed to promote the wide application of this technology in the diagnosis and treatment of depression.