Suchting Robert, Razouq Dana, Jose Lijin, Nascimento E Silva Flavio, Wardle Margaret C, Soares Jair C, Teixeira Antonio L, Selvaraj Sudhakar
Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA.
Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA.
J Psychiatr Res. 2023 May;161:106-111. doi: 10.1016/j.jpsychires.2023.03.019. Epub 2023 Mar 9.
Acute inflammation is associated with sickness behavior characterized by reduced motivation for pleasurable activities in humans. The current study investigated the effect of an experimentally induced inflammatory stimulus on motivational reward in people who remitted from depression.
This randomized, double-blind crossover study involved 12 participants, 5 with remitted major depressive disorder (rMDD) and 7 healthy controls (HC), who received an injection of typhoid vaccine and placebo (or vice-versa) intramuscularly at least one week apart. At baseline and between 4 and 6 h post-injection on both days, participant mood was measured using the profile of mood states (POMS), and injection blood samples were collected for cytokines measurement. All participants completed the Effort Expenditure for Rewards Task (EEfRT), a behavioral paradigm measuring effort-based decision-making before and 4 h post-both injections. Generalized linear mixed modeling was used to evaluate group differences in choosing the hard over easy task to obtain a monetary reward.
Typhoid vaccine increased IL-6 in all participants. On the EEfRT, a significant interaction between treatment condition (typhoid vs. placebo) and participant group (HC vs. rMDD) was found (p = .004). Analyses of simple effects within treatment conditions found that after placebo, HCs were more likely to choose the harder task than rMDD (OR = 3.21; p = .013). However, after the typhoid vaccine, no differences were found between rMDD and HC (p = .397). Analyses within participant groups found that the probability of choosing a hard task was higher after placebo for HC (OR = 1.37; p = .045), but not different within rMDD (p = .241). For HC at baseline, mood was significantly lower following injection with typhoid vaccine, relative to placebo (b = -1.03, p < .001); however, this effect should be considered coincidental, given that mood rating was taken prior to injection. For rMDD patients 4-6 h post-injection, mood was significantly lower following typhoid vaccine, relative to placebo (b = -0.981, p < .001 b = -0.77, p < .001). Finally, for HC receiving placebo, mood was significantly lower 4-6 h post-injection, relative to baseline (b = -1.76, p < .001).
Our preliminary findings suggest persistent deficits in motivational reward processing function despite clinical improvement in remitted depressed patients.
急性炎症与疾病行为有关，其特征是人类对愉悦活动的动机降低。本研究调查了实验诱导的炎症刺激对抑郁症缓解者动机奖赏的影响。
这项随机、双盲交叉研究涉及12名参与者，其中5名是缓解期重度抑郁症（rMDD）患者，7名是健康对照者（HC），他们至少间隔一周接受一次肌肉注射伤寒疫苗和安慰剂（或反之）。在基线时以及两天注射后4至6小时，使用情绪状态剖面图（POMS）测量参与者的情绪，并采集注射后的血样进行细胞因子测量。所有参与者在两次注射前和注射后4小时完成奖励任务的努力支出（EEfRT），这是一种测量基于努力的决策的行为范式。使用广义线性混合模型评估在选择困难任务而非简单任务以获得金钱奖励方面的组间差异。
伤寒疫苗使所有参与者的白细胞介素-6升高。在EEfRT上，发现治疗条件（伤寒疫苗与安慰剂）和参与者组（HC与rMDD）之间存在显著交互作用（p = 0.004）。对治疗条件内简单效应的分析发现，注射安慰剂后，HC比rMDD更有可能选择较难的任务（OR = 3.21；p = 0.013）。然而，注射伤寒疫苗后，rMDD和HC之间没有差异（p = 0.397）。在参与者组内的分析发现，HC在注射安慰剂后选择困难任务的概率更高（OR = 1.37；p = 0.045），但在rMDD组内没有差异（p = 0.241）。对于基线时的HC，注射伤寒疫苗后的情绪相对于安慰剂显著降低（b = -1.03，p < .001）；然而，鉴于情绪评分是在注射前进行的，这种效应应被视为巧合。对于注射后4 - 6小时的rMDD患者，伤寒疫苗后的情绪相对于安慰剂显著降低（b = -0.981，p < .001；b = -0.77，p < .001）。最后，对于接受安慰剂的HC，注射后4 - 6小时的情绪相对于基线显著降低（b = -1.76，p < .001）。
我们的初步研究结果表明，尽管缓解期抑郁症患者临床症状有所改善，但在动机奖赏处理功能方面仍存在持续缺陷。
