Abstract：
BACKGROUND: Research suggests structural and connectivity abnormalities in patients with treatment-resistant schizophrenia (TRS) compared to first-line responders and healthy-controls. However, measures of these abnormalities are often influenced by external factors like nicotine and antipsychotics, limiting their clinical utility. Intrinsic-cortical-curvature (ICC) presents a millimetre-scale measure of brain gyrification, highly sensitive to schizophrenia differences, and associated with TRS-like traits in early stages of the disorder. Despite this evidence, ICC in TRS remains unexplored. This study investigates ICC as a marker for treatment resistance in TRS, alongside structural indices for comparison.
METHODS: We assessed ICC in anterior cingulate, dorsolateral prefrontal, temporal, and parietal cortices of 38 first-line responders, 30 clozapine-resistant TRS, 37 clozapine-responsive TRS, and 52 healthy-controls. For comparative purposes, Fold and Curvature indices were also analyzed.
RESULTS: Adjusting for age, sex, nicotine-use, and chlorpromazine equivalence, principal findings indicate ICC elevations in the left hemisphere dorsolateral prefrontal (p < 0.001, η2partial = 0.142) and temporal cortices (LH p = 0.007, η2partial = 0.060; RH p = 0.011, η2partial = 0.076) of both TRS groups, and left anterior cingulate cortex of clozapine-resistant TRS (p = 0.026, η2partial = 0.065), compared to healthy-controls. Elevations that correlated with reduced cognition (p = 0.001) and negative symptomology (p < 0.034) in clozapine-resistant TRS. Fold and Curvature indices only detected group differences in the right parietal cortex, showing interactions with age, sex, and nicotine use. ICC showed interactions with age.
CONCLUSIONS: ICC elevations were found among patients with TRS, and correlated with symptom severity. ICCs relative independence from sex, nicotine-use, and antipsychotics, may support ICC\'s potential as a viable marker for TRS, though age interactions should be considered.
METHODS: We assessed ICC in anterior cingulate, dorsolateral prefrontal, temporal, and parietal cortices of 38 first-line responders, 30 clozapine-resistant TRS, 37 clozapine-responsive TRS, and 52 healthy-controls. For comparative purposes, Fold and Curvature indices were also analyzed.
RESULTS: Adjusting for age, sex, nicotine-use, and chlorpromazine equivalence, principal findings indicate ICC elevations in the left hemisphere dorsolateral prefrontal (p < 0.001, η2partial = 0.142) and temporal cortices (LH p = 0.007, η2partial = 0.060; RH p = 0.011, η2partial = 0.076) of both TRS groups, and left anterior cingulate cortex of clozapine-resistant TRS (p = 0.026, η2partial = 0.065), compared to healthy-controls. Elevations that correlated with reduced cognition (p = 0.001) and negative symptomology (p < 0.034) in clozapine-resistant TRS. Fold and Curvature indices only detected group differences in the right parietal cortex, showing interactions with age, sex, and nicotine use. ICC showed interactions with age.
CONCLUSIONS: ICC elevations were found among patients with TRS, and correlated with symptom severity. ICCs relative independence from sex, nicotine-use, and antipsychotics, may support ICC\'s potential as a viable marker for TRS, though age interactions should be considered.
摘要：
背景：研究表明，与一线反应者和健康对照者相比，难治性精神分裂症（TRS）患者的结构和连接异常。然而,这些异常的测量通常受到尼古丁和抗精神病药等外部因素的影响，限制其临床效用。内在皮质曲率（ICC）提供了一种毫米级的脑旋化测量，对精神分裂症的差异高度敏感，并与疾病早期的TRS样特征相关。尽管有这些证据,TRS中的ICC仍未开发。这项研究调查了ICC作为TRS治疗抵抗的标志物，与结构指数进行比较。
方法：我们评估了前扣带的ICC，背外侧前额叶,temporal,和38名一线反应者的顶骨皮质，30氯氮平耐药TRS，37氯氮平反应性TRS，和52个健康对照。出于比较目的，还分析了折叠和曲率指数。
结果：调整年龄，性别,尼古丁的使用,和氯丙嗪等效，主要发现表明两个TRS组的左半球背外侧前额叶（p<0.001，η2部分=0.142）和颞皮质（LHp=0.007，η2部分=0.060；RHp=0.011，η2部分=0.076）的ICC升高，氯氮平耐药TRS的左前扣带回皮质（p=0.026，η2部分=0.065），与健康对照相比。与氯氮平耐药TRS的认知降低（p=0.001）和阴性症状学（p<0.034）相关的升高。折叠和曲率指数仅检测到右侧顶叶皮层的组差异，显示与年龄的互动，性别,尼古丁的使用。ICC显示与年龄的相互作用。
结论：在TRS患者中发现ICC升高，并与症状严重程度相关。ICC相对独立于性别，尼古丁的使用,和抗精神病药，可能支持ICC作为TRS可行标记的潜力，虽然年龄的相互作用应该被考虑。
方法：我们评估了前扣带的ICC，背外侧前额叶,temporal,和38名一线反应者的顶骨皮质，30氯氮平耐药TRS，37氯氮平反应性TRS，和52个健康对照。出于比较目的，还分析了折叠和曲率指数。
结果：调整年龄，性别,尼古丁的使用,和氯丙嗪等效，主要发现表明两个TRS组的左半球背外侧前额叶（p<0.001，η2部分=0.142）和颞皮质（LHp=0.007，η2部分=0.060；RHp=0.011，η2部分=0.076）的ICC升高，氯氮平耐药TRS的左前扣带回皮质（p=0.026，η2部分=0.065），与健康对照相比。与氯氮平耐药TRS的认知降低（p=0.001）和阴性症状学（p<0.034）相关的升高。折叠和曲率指数仅检测到右侧顶叶皮层的组差异，显示与年龄的互动，性别,尼古丁的使用。ICC显示与年龄的相互作用。
结论：在TRS患者中发现ICC升高，并与症状严重程度相关。ICC相对独立于性别，尼古丁的使用,和抗精神病药，可能支持ICC作为TRS可行标记的潜力，虽然年龄的相互作用应该被考虑。
