BACKGROUND Immune dysfunction has been implicated in negative symptoms of schizophrenia and also in depression. These disorders are frequently co-morbid, with some symptoms such as anhedonia and apathy common to both. The anti-inflammatory agent minocycline may be ineffective in schizophrenia, but more positive effects have been seen in depression. Our aim was to investigate the role of immune dysfunction in depression and sub-domains of negative symptoms in schizophrenia by investigating their intercorrelation and the influence of treatment with minocycline. METHODS We analysed longitudinal data from 207 patients within 5 years of onset of schizophrenia, from the randomised double-blind, placebo-controlled trial of minocycline (BeneMin). Symptom ratings and circulating IL-6, C-reactive protein (CRP) and TNF-α concentrations were collected at baseline and repeated over twelve months. The sample was not stratified by CRP prior to randomisation. Positive and Negative Syndrome Scale composite ratings of avolition-apathy and diminished expression, Calgary Depression Scale total scores, and immune markers were examined cross-sectionally using Spearman's rank, and longitudinally by linear mixed effect models that included body mass index and minocycline. Additionally, post hoc analysis of the sample stratified by elevated CRP (>1 mg/l and <10 mg/l at baseline) was carried out to assess whether minocycline had any effect on specific symptoms in an immune active sub-group of patients. RESULTS Depression and avolition-apathy were significantly positively related, and depression correlated weakly with IL-6 at baseline. Diminished expression was associated with increased TNF-α both cross-sectionally and longitudinally. CRP was unrelated to any symptom domain. Minocycline did not affect any individual symptom or sub-domain in the full sample or in the immune active sub-group. DISCUSSION IL-6 may have some specificity to depression in early schizophrenia. TNF-α may be an indicator of immune dysfunction relevant to negative symptoms, and our longitudinal findings add to this evidence. However, minocycline continues to show very little promise as a treatment for any symptom dimension of early schizophrenia.

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解构精神分裂症的抑郁和阴性症状；差异和纵向免疫相关性，以及对米诺环素治疗的反应

背景技术免疫功能障碍与精神分裂症的阴性症状以及抑郁症有关。这些疾病通常是共病的，两者都有一些症状，例如快感缺乏和冷漠。抗炎药米诺环素可能对精神分裂症无效，但在抑郁症中观察到了更积极的作用。我们的目的是通过调查免疫功能障碍在抑郁症和精神分裂症阴性症状亚域中的相互关系和米诺环素治疗的影响来研究它们的作用。方法 我们分析了来自米诺环素 (BeneMin) 的随机双盲、安慰剂对照试验的 207 名精神分裂症发病 5 年内的患者的纵向数据。症状评级和循环 IL-6，在基线收集 C 反应蛋白 (CRP) 和 TNF-α 浓度并在十二个月内重复。在随机化之前，样本没有按 CRP 分层。使用 Spearman 等级横向检查和纵向检查包括体重指数和米诺环素在内的线性混合效应模型，对意志冷漠和表达减少、卡尔加里抑郁量表总分和免疫标志物的阳性和阴性综合征量表综合评分。此外，对按升高的 CRP（基线时>1 mg/l 和 <10 mg/l）分层的样本进行了事后分析，以评估米诺环素是否对免疫活性亚组患者的特定症状有任何影响。结果抑郁和意志冷漠显着正相关，抑郁与基线时的IL-6弱相关。减少的表达与横断面和纵向的 TNF-α 增加有关。CRP 与任何症状域无关。米诺环素不影响完整样本或免疫活性亚组中的任何个体症状或亚域。讨论 IL-6 可能对早期精神分裂症的抑郁症有一定的特异性。TNF-α 可能是与阴性症状相关的免疫功能障碍的指标，我们的纵向研究结果增加了这一证据。然而，米诺环素作为早期精神分裂症任何症状维度的治疗方法仍然没有多大希望。讨论 IL-6 可能对早期精神分裂症的抑郁症有一定的特异性。TNF-α 可能是与阴性症状相关的免疫功能障碍的指标，我们的纵向研究结果增加了这一证据。然而，米诺环素作为早期精神分裂症任何症状维度的治疗方法仍然没有多大希望。讨论 IL-6 可能对早期精神分裂症的抑郁症有一定的特异性。TNF-α 可能是与阴性症状相关的免疫功能障碍的指标，我们的纵向研究结果增加了这一证据。然而，米诺环素作为早期精神分裂症任何症状维度的治疗方法仍然没有多大希望。