Department of Psychiatry, Neuropsychiatry Division, Perelman School of Medicine, University of Pennsylvania, PA 19104, United States; Smell and Taste Center, Department of Otorhinolaryngology: Head & Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Department of Psychiatry, Neuropsychiatry Division, Perelman School of Medicine, University of Pennsylvania, PA 19104, United States; Smell and Taste Center, Department of Otorhinolaryngology: Head & Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Schizophr Res. 2018 May;195:197-205. doi: 10.1016/j.schres.2017.09.015. Epub 2017 Sep 30.
Olfactory impairments are prominent in both schizophrenia and the preceding at-risk state. Their presence prior to illness predicts poor functional outcome. In schizophrenia, these impairments reflect peripheral olfactory structural abnormalities, which are hypothesized to arise during early embryonic development. If this is correct, then similar structural anomalies should be apparent among clinical high-risk subjects.
Thirty-nine clinical high-risk (CR) subjects (24M/15F) were compared to 36 low-risk (LR) subjects (19M/17F). Olfactory measures derived from 3T MRI scans included olfactory bulb volume, primary olfactory cortical gray matter volume, and the depth of the olfactory sulcus overlying the bulb. Additionally, nasal cavity volumes were assessed with acoustic rhinometry.
Male CR subjects exhibited bilateral reductions in olfactory bulb volume and abnormal asymmetries of the posterior nasal cavities and olfactory sulci (left reduced relative to right). Post-hoc contrasts also indicated reduced left, but not right, olfactory cortical gray matter volume. Female CRs had no significant abnormalities, although they exhibited similar trend effects. Left olfactory bulb volume correlated, across all CR subjects, with negative, but not positive, symptoms. In a classification analysis, with 80% target specificity, olfactory measurements distinguished male CR from male LR subjects with 93% sensitivity. Among females, the comparable sensitivity was 69%.
Psychosis-risk youths exhibit an array of sexually dimorphic and laterally asymmetric anomalies of the peripheral olfactory system. These are consistent with a developmental disruption primarily affecting male fetuses. These structural biomarkers may enhance the identification of at-risk subjects with poor prognosis, before their clinical trajectory is apparent.
嗅觉障碍在精神分裂症和发病前的高危状态中都很突出。疾病发生前的存在预示着较差的功能预后。在精神分裂症中，这些损伤反映了外周嗅觉结构异常，这些异常被假设是在胚胎早期发育过程中产生的。如果这是正确的，那么类似的结构异常应该在临床高危人群中显现出来。
将 39 名临床高危（CR）受试者（24 名男性/15 名女性）与 36 名低危（LR）受试者（19 名男性/17 名女性）进行比较。3T MRI 扫描得出的嗅觉测量包括嗅球体积、初级嗅皮质灰质体积以及嗅球上方嗅沟的深度。此外，还使用声学鼻反射计评估鼻腔体积。
男性 CR 受试者表现出双侧嗅球体积减少，以及后鼻腔和嗅沟的异常不对称（左侧相对右侧减少）。事后对比还表明，左侧嗅皮质灰质体积减少，但右侧没有。女性 CR 没有明显异常，尽管她们表现出类似的趋势效应。所有 CR 受试者的左侧嗅球体积与阴性但非阳性症状相关。在分类分析中，以 80%的目标特异性，嗅觉测量将男性 CR 与男性 LR 受试者区分开来，敏感性为 93%。在女性中，类似的敏感性为 69%。
精神病风险青少年表现出一系列与性别有关的和不对称的外周嗅觉系统异常。这些异常与主要影响男性胎儿的发育中断一致。这些结构生物标志物可能会在临床轨迹明显之前，增强对预后不良的高危人群的识别。
