Salisbury Dean F, Kuroki Noriomi, Kasai Kiyoto, Shenton Martha E, McCarley Robert W
Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Boston, MA, USA.
Arch Gen Psychiatry. 2007 May;64(5):521-9. doi: 10.1001/archpsyc.64.5.521.
Progressive brain abnormalities in schizophrenia remain controversial. Evidence of interrelated progressive functional impairment would buttress the case for structural progression. Mismatch negativity (MMN) is reduced in chronic but not first-hospitalized schizophrenia and may index progressive structural changes.
To determine whether MMN shows associations with underlying auditory cortex gray matter at first hospitalization and progressive reduction longitudinally.
Cross-sectional (first hospitalization) and longitudinal (1.5-year follow-up).
A private psychiatric hospital.
Protocol entrance: MMN and magnetic resonance imaging at first hospitalization in 20 subjects with schizophrenia, 21 subjects with bipolar disorder with psychosis, and 32 control subjects. Longitudinal electrophysiologic testing: MMN in 16 subjects with schizophrenia, 17 subjects with bipolar disorder, and 20 control subjects. Longitudinal electrophysiologic testing and magnetic resonance imaging: MMN and magnetic resonance imaging in 11 subjects with schizophrenia, 13 subjects with bipolar disorder, and 13 control subjects. At each time point, reported samples were group matched for age, handedness, and parental socioeconomic status.
Electrophysiologic testing and high-resolution structural magnetic resonance imaging.
Mismatch negativity amplitude and Heschl gyrus and planum temporale gray matter volumes.
Initially, groups did not differ in MMN amplitude. Subjects with schizophrenia showed associations between MMN and Heschl gyrus (r=-0.52; P=.02) not present in the other groups. At longitudinal MMN testing, schizophrenia showed MMN reduction (P=.004). Only schizophrenia evinced longitudinal left hemisphere Heschl gyrus reduction (P=.003), highly correlated with MMN reduction (r=0.6; P=.04).
At first hospitalization for schizophrenia, MMN indexed left hemisphere Heschl gyrus gray matter volume, consistent with variable progression of pre-hospitalization cortical reduction. Longitudinally, the interrelated progressive reduction of functional and structural measures suggests progressive pathologic processes early in schizophrenia. An active process of progressive cortical reduction presents a potential therapeutic target. Mismatch negativity may be a simple, sensitive, and inexpensive index not only of this progressive pathologic process but also of successful intervention.
精神分裂症中进行性脑异常仍存在争议。相关进行性功能损害的证据将支持结构进展的观点。失匹配负波（MMN）在慢性精神分裂症患者中降低，但首次住院患者中未降低，可能提示进行性结构变化。
确定MMN在首次住院时是否与听觉皮层灰质相关，以及纵向是否逐渐降低。
横断面研究（首次住院）和纵向研究（1.5年随访）。
一家私立精神病医院。
研究开始时：20例精神分裂症患者、21例伴有精神病性症状的双相情感障碍患者和32例对照者在首次住院时进行MMN和磁共振成像检查。纵向电生理测试：16例精神分裂症患者、17例双相情感障碍患者和20例对照者进行MMN测试。纵向电生理测试和磁共振成像：11例精神分裂症患者、13例双相情感障碍患者和13例对照者进行MMN和磁共振成像检查。在每个时间点，报告的样本在年龄、利手和父母社会经济地位方面进行组间匹配。
电生理测试和高分辨率结构磁共振成像。
失匹配负波幅值以及颞横回和颞平面灰质体积。
最初，各组MMN幅值无差异。精神分裂症患者中MMN与颞横回存在相关性（r=-0.52；P=0.02），其他组不存在这种相关性。在纵向MMN测试中，精神分裂症患者的MMN降低（P=0.004）。只有精神分裂症患者出现纵向左侧颞横回体积减小（P=0.003），且与MMN降低高度相关（r=0.6；P=0.04）。
在精神分裂症首次住院时，MMN可反映左侧颞横回灰质体积，这与住院前皮层减少的可变进展一致。纵向来看，功能和结构指标的相关进行性降低提示精神分裂症早期存在进行性病理过程。进行性皮层减少的活跃过程是一个潜在的治疗靶点。失匹配负波可能不仅是这种进行性病理过程的一个简单、敏感且廉价的指标，也是成功干预的指标。
