There are many subtypes of major depressive disorder (MDD) . Evidence about the differentiation of them is mostly based on symptomatological characteristics, but rarely by objective biological indicators.

To explore the differences in event-related potential (ERP) N400 between patients with different subtypes of depression, providing an objective electrophysiological basis for subtyping depression.

Two hundred and nine outpatients and inpatients who met the diagnostic criteria of MDD in Diagnostic and Statistical Manual of Mental Disorders, 5th Edition were selected from First Hospital of Shanxi Medical University from February 2019 to December 2021, including 78 with anxious depression (ASD+MD-) , 46 with melancholic depression (ASD-MD+) , 61 with anxious and melancholic depression (ASD+MD+) , and 24 with non-anxious and melancholic depression (ASD-MD-) subtyped using the 30-item Inventory of Depressive Symptomatology (IDS-30) and 17-item Hamilton Depression Rating Scale (HAMD-17) . Thirty-five community-living health volunteers were recruited as controls at the same time.The factor and total scores of the HAMD-17 and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) of all subjects were collected. And the latency and amplitude of N400 component of all subjects were collected by inducing N400 components through understanding ambiguous words at the end of sentences.

(1) The total score and factor scores of HAMD-17 differed significantly across MDD subgroups and control group (P< 0.05) . The total score of HAMD-17 in each of the four MDD subgroups was much higher than that in control group (P<0.05) . ASD+MD+ subgroup had significantly higher total score of HAMD-17 than both ASD-MD- and ASD-MD+ subgroups (P<0.05) .ASD+MD- subgroup had significantly higher total score of HAMD-17 than ASD-MD+ subgroup (P<0.05) . The score of anxiety factor in each of the four MDD subgroups was obviously higher than that in control group (P<0.05) . ASD+MD- subgroup had obviously higher score of anxiety factor than both ASD-MD+ and ASD-MD- subgroups (P<0.05) .ASD+MD+ subgroup had prominently higher score of anxiety factor than both ASD-MD+ and ASD-MD- subgroups (P < 0.05) . The score of body weight factor in ASD+MD+ or ASD+MD- subgroup was much higher than that in control group (P<0.05) .ASD+MD+ subgroup had much higher score of body weight factor than both ASD-MD- and ASD-MD+ subgroups (P<0.05) . The score of cognitive impairment factor in each of the four MDD subgroups was much higher than that in control group (P<0.05) .ASD+MD+ subgroup had much higher score of cognitive impairment factor than ASD-MD+ subgroup (P<0.05) . The scores of block factor and sleep disturbance factor in each of the four MDD subgroups were significantly higher than those in the control group (P<0.05) . (2) The total score and factor scores of RBANS varied significantly across four MDD subgroups and control group (P<0.05) .The total score of RBANS and scores of its factors of immediate memory, visual span, speech function, attention, and delayed memory in each of the four MDD subgroups were much lower than those in the control group (P<0.05) . The score of immediate memory factor in ASD+MD+ group was notably lower than that in ASD-MD+ group (P<0.05) . (3) There were no significant differences in latency and amplitude of N400 component across four MDD subgroups and controls (P>0.05) .There were no significant differences in latency and amplitude of N400 component across different electrode sites (P>0.05) , and there were no interaction between no-depression or each of the four subtypes of MDD and electrode sites (P>0.05) . (4) The N400 amplitude value at Fz electrode was negatively correlated with the cognitive impairment factor score (r=-0.170, P=0.016) .The N400 amplitude value at Cz electrode was positively correlated with the block factor score (r=0.151, P=0.033) .The N400 amplitude valueat Pz electrode was positively correlated with the block factor score (r=0.174, P=0.014) .The N400 amplitude value of the Fz electrode was positively correlated with the immediate memory score (r=0.138, P=0.050) .The N400 latency value at Cz electrode was negatively correlated with the delayed memory score (r=-0.155, P=0.028) .

Extensive cognitive impairment was found in MDD patients, including impaired immediate memory, speech function, attention and delayed memory. ASD+MD+ and ASD+ MD-patients had more severe symptoms, and ASD+MD+ patients had the most severe cognitive impairment. N400 amplitude value was negatively correlated with cognitive impairment and positively correlated with block factor in MDD patients. But these patients demonstrated no impaired function of speech integration induced by ambiguous words at the end of sentences.

重性抑郁障碍（MDD）包含多种亚型，目前亚型区分多基于症状学特征，缺乏客观的生物学指标。

探究不同抑郁亚型患者事件相关电位（ERP）N400的差异，为抑郁亚型分型提供客观电生理依据。

选取2019年2月至2021年12月山西医科大学第一医院精神卫生科门诊或住院部符合《精神障碍诊断与统计手册第5版》中MDD诊断标准的患者，采用30项抑郁障碍症状量表（IDS-30）、17项汉密尔顿抑郁量表（HAMD-17）对患者进行亚型分型，最终纳入78例单纯焦虑型MDD（ASD+MD-组）、46例单纯忧郁型MDD（ASD-MD+组）、61例焦虑忧郁型MDD（ASD+MD+组）、24例非焦虑忧郁型MDD（ASD-MD-组），同期招募社区健康志愿者35例作为对照组。评估所有受试者HAMD-17、重复性成套神经心理状态测验（RBANS）的总分及因子分；通过句末歧义词诱发N400成分，采集所有受试者N400的潜伏期及波幅。

（1）MDD各亚组及对照组的HAMD-17总分及各因子分比较，差异均有统计学意义（P<0.05），其中HAMD-17总分MDD各亚组均高于对照组，ASD+MD+组高于ASD-MD+组和ASD-MD-组，ASD+MD-组高于ASD-MD+组，差异均有统计学意义（P<0.05）；焦虑因子分MDD各亚组均高于对照组，ASD+MD-组高于ASD-MD+组、ASD-MD-组，ASD+MD+组高于ASD-MD+组、ASD-MD-组，差异均有统计学意义（P<0.05）；体重因子分ASD+MD+组、ASD+MD-组均高于对照组，ASD+MD+组高于ASD-MD+组、ASD-MD-组，差异均有统计学意义（P<0.05）；认知障碍因子分MDD各亚组均高于对照组，ASD+MD+组高于ASD-MD+组，差异均有统计学意义（P<0.05）；MDD各亚组的阻滞因子分、睡眠障碍因子分均高于对照组，差异有统计学意义（P<0.05）。（2）MDD各亚型组及对照组的RBANS总分及各因子分比较，差异均有统计学意义（P<0.05），MDD各亚组的即刻记忆、视觉广度、言语功能、注意、延时记忆因子分及RBANS总分均低于对照组（P<0.05）；ASD+MD+组的即刻记忆因子分低于ASD-MD+组（P<0.05）。（3）不同组别间潜伏期、波幅的差异无统计学意义（P>0.05），不同电极点间潜伏期、波幅的差异无统计学意义（P>0.05），且组别与电极点间无交互作用（P>0.05）。（4）中线前额电极点（Fz）的N400波幅与认知障碍因子分呈负相关（r=-0.170，P=0.016），中线中央区电极点（Cz）的波幅与阻滞因子分呈正相关（r=0.151，P=0.033），中线顶区电极点（Pz）的波幅与阻滞因子分呈正相关（r=0.174，P=0.014）；Fz的N400波幅与即刻记忆分呈正相关（r=0.138，P=0.050），Cz的潜伏期与延时记忆因子分呈负相关（r=-0.155，P=0.028）。

MDD患者存在广泛认知功能损害，即刻记忆、视觉广度、言语功能、注意、延时记忆能力均低于正常人，在各个亚型中ASD+MD+亚型及ASD+MD-亚型患者症状较重，ASD+MD+亚型患者认知功能损害最明显。MDD患者N400波幅与认知障碍呈负相关，与阻滞因子呈正相关。但MDD患者由句末歧义词诱发的言语整合功能未受损害。