Abstract:

The early detection of major depressive disorder (MDD) is critical for timely intervention and better outcomes of treatment. Extensive efforts have been made to evaluate methods of detecting MDD in its early stages of development. Methods that have been empirically shown promising can be roughly classified into three categories, focusing on the prodromal symptoms, the risk factors , and the biological endophenotype of MDD. The prodromal approach identifies individuals with early MDD through the screening prodromal symptoms, such as insomnia, fatigue, difficulty in concentrating, indecision, contemplation, lack of self-confidence, decreased efficiency, helplessness, reduced motivation, tension, irritability, physical discomfort, decreased energy, loss of appetite, gastrointestinal disorders, and so on. The estimated duration of the prodromal period varies across studies, spanning between 6 weeks to 23 months. In most studies, early depressive symptoms were identified by means of clinical interview or mental symptom rating. The second approach, which aims at determining individuals’ susceptibility to MDD, emphasizes the importance of examining the family history and personal risk factors of potential MDD patients. Family history is a major risk factor for MDD. If a first-degree relative has MDD, the chance of an individual developing this disorder is about 10-13%. As for personal risk factors, they could be either cognitive or emotional. Studies have shown that the first-degree relatives of MDD patients are more likely to have negative cognitive biases, and they show low level of positive emotions. A third and promising approach focuses on identifying potential biological markers of MDD. Previous neuroimaging studies have shown that MDD patients have abnormalities in brain structure and function. The dorsal anterolateral prefrontal cortex and the anterior cingulate cortex of MDD patients are reduced in volume. In addition, MDD patients also have reduced activity in the ventral striatum, increased activity of the thalamus in the positive condition, increased activity in cortical midline structures, increased connectivity in the default mode network (DMN), decreased regional homogeneity (ReHo) in the left insula and left cerebellum, shortened latency and increased density of REM sleep. Furthermore, previous studies have found that MMD patients have increased activity in the hypothalamic-pituitary-adrenocortical (HPA) axis, and lowered concentration level of neurotransmitters, such as serotonin, catecholamines, tryptophan, and γ-aminobutyric acid, in some neural pathways and brain regions. These three approaches are all successful, to varied extend, in detecting early stage patients of MDD. However, one needs to be mindful of the disadvantages of these research approaches. The prodromal approach is phenomenological in nature, the prodromal symptoms usually lacks specificity and the methods used to identify them are too often subjective. Longitudinal studies that focus on individuals’ susceptibility to MDD is scarce in the literature; it remains unclear how various family and personal risk factors collaborate to deliver the end result of MDD. In clinical situations, it is not possible for a psychiatrist to make diagnoses based solely on these risk factors. As for the biological endophenotype approach, most previous studies have examined clinical stage patients rather than those in the early stages of developing MDD. Thus, it is difficult to determine which of the identified biomarkers are reliable warning signs of MDD. To identify reliable and objective precursors of MDD and to build an accurate risk prediction model, future studies should consider the use of high risk family designs to trace down the biological endophenotype of MDD.

摘要：

抑郁症早期识别技术至今仍未解决，需要厘清研究思路。回顾以往研究可梳理出三类方法，即：前驱症状法、易感性法、生物内表型法。前驱症状法是依据前驱期症状识别早期患者，但现象学指标的客观性和特异性较差；易感性法是依据家系或个体风险因素界定风险人群，但缺少纵向研究支持，很难直接用于预警；生物内表型法是寻找与疾病相关的潜在生物学标记，但多为临床期研究，不能确定其中哪些可作为前驱期征象。今后的研究可考虑整合三类方法，即利用家系高风险设计寻找生物内表型，并以此识别可靠前驱症状，构建更精确的风险预测模型。