Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
Psychol Med. 2023 Mar;53(4):1479-1488. doi: 10.1017/S0033291721003056. Epub 2021 Aug 11.
Both neurodegenerative and neurodevelopmental abnormalities have been suggested to be part of the etiopathology of severe mental illness (SMI). Neuron-specific enolase (NSE), mainly located in the neuronal cytoplasm, may indicate the process as it is upregulated after neuronal injury while a switch from non-neuronal enolase to NSE occurs during neuronal maturation.
We included 1132 adult patients with SMI [schizophrenia (SZ) or bipolar spectrum disorders], 903 adult healthy controls (HC), 32 adolescent patients with SMI and 67 adolescent HC. Plasma NSE concentrations were measured by enzyme immunoassay. For 842 adults and 85 adolescents, we used total grey matter volume (TGMV) based on T1-weighted magnetic resonance images processed in FreeSurfer v6.0. We explored NSE case-control differences in adults and adolescents separately. To investigate whether putative case-control differences in NSE were TGMV-dependent we controlled for TGMV.
We found significantly lower NSE concentrations in both adult ( < 0.001) and adolescent patients with SMI ( = 0.007) compared to HC. The results remained significant after controlling for TGMV. Among adults, both patients with SZ spectrum ( < 0.001) and bipolar spectrum disorders ( = 0.005) had lower NSE than HC. In both patient subgroups, lower NSE levels were associated with increased symptom severity. Among adults ( < 0.001) and adolescents ( = 0.040), females had lower NSE concentrations than males.
We found lower NSE concentrations in adult and adolescent patients with SMI compared to HC. The results suggest the lack of progressive neuronal injury, and may reflect abnormal neuronal maturation. This provides further support of a neurodevelopmental rather than a neurodegenerative mechanism in SMI.
神经退行性和神经发育异常都被认为是严重精神疾病（SMI）发病机制的一部分。神经元特异性烯醇化酶（NSE）主要位于神经元细胞质中，在神经元损伤后上调，而在神经元成熟过程中会发生从非神经元烯醇化酶到 NSE 的转换，因此它可能表明这一过程。
我们纳入了 1132 名成年 SMI 患者（精神分裂症或双相谱系障碍）、903 名成年健康对照者（HC）、32 名青少年 SMI 患者和 67 名青少年 HC。通过酶联免疫吸附法测定血浆 NSE 浓度。对于 842 名成年人和 85 名青少年，我们使用基于 T1 加权磁共振图像的总灰质体积（TGMV），并在 FreeSurfer v6.0 中进行处理。我们分别在成年人和青少年中探索 NSE 的病例对照差异。为了研究 NSE 的潜在病例对照差异是否依赖于 TGMV，我们对 TGMV 进行了控制。
我们发现成年（<0.001）和青少年（=0.007）SMI 患者的 NSE 浓度显著低于 HC。在控制 TGMV 后，结果仍然显著。在成年人中，精神分裂症谱系（<0.001）和双相谱系障碍（=0.005）患者的 NSE 均低于 HC。在两个患者亚组中，较低的 NSE 水平与症状严重程度增加有关。在成年人（<0.001）和青少年（=0.040）中，女性的 NSE 浓度低于男性。
我们发现成年和青少年 SMI 患者的 NSE 浓度低于 HC。结果表明缺乏进行性神经元损伤，可能反映了异常的神经元成熟。这进一步支持了 SMI 中的神经发育机制而非神经退行性机制。
