Kristensen Tina D, Ebdrup Bjørn H, Hjorthøj Carsten, Mandl René C W, Raghava Jayachandra M, Jepsen Jens Richardt M, Fagerlund Birgitte, Glenthøj Louise B, Wenneberg Christina, Krakauer Kristine, Pantelis Christos, Glenthøj Birte Y, Nordentoft Merete
Copenhagen Research Center for Mental Health, CORE, Mental Health Centre Copenhagen, University of Copenhagen, Hellerup, Denmark.
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
Front Psychiatry. 2020 Aug 28;11:873. doi: 10.3389/fpsyt.2020.00873. eCollection 2020.
Individuals at ultra-high risk for psychosis (UHR) present with subtle alterations in cerebral white matter (WM), which appear to be associated with clinical and functional outcome. The effect of cognitive remediation on WM organization in UHR individuals has not been investigated previously.
In a randomized, clinical trial, UHR individuals aged 18 to 40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation for 20 weeks. Cognitive remediation comprised 20 x 2-h sessions of neurocognitive and social-cognitive training. Primary outcome was whole brain fractional anisotropy derived from diffusion weighted imaging, statistically tested as an interaction between timepoint and treatment group. Secondary outcomes were restricted to five predefined region of interest (ROI) analyses on fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity. For significant timepoint and treatment group interactions within these five ROIs, we explored associations between longitudinal changes in WM and cognitive functions/clinical symptoms. Finally, we explored dose-response effects of cognitive remediation on WM.
A total of 111 UHR individuals were included. Attrition-rate was 26%. The cognitive remediation group completed on average 12 h of neurocognitive training, which was considerably lower than per protocol. We found no effect of cognitive remediation on whole-brain FA when compared to treatment as usual. Secondary ROI analyses revealed a nominal significant interaction between timepoint*treatment of AD in left medial lemniscus (P=0.016) which did not survive control for multiple comparisons. The exploratory test showed that this change in AD correlated to improvements of mental flexibility in the cognitive remediation group (p=0.001). We found no dose-response effect of neurocognitive training on WM.
Cognitive remediation comprising 12 h of neurocognitive training on average did not improve global or regional WM organization in UHR individuals. Further investigations of duration and intensity of cognitive training as necessary prerequisites of neuroplasticity-based changes are warranted.
ClinicalTrials.gov, identifier NCT02098408.
超高危精神病个体（UHR）的脑白质（WM）存在细微改变，这似乎与临床和功能结局相关。认知康复对UHR个体WM组织的影响此前尚未得到研究。
在一项随机临床试验中，将18至40岁的UHR个体分配至常规治疗（TAU）组或TAU加认知康复组，为期20周。认知康复包括20次每次2小时的神经认知和社会认知训练。主要结局是通过扩散加权成像得出的全脑分数各向异性，作为时间点与治疗组之间的相互作用进行统计学检验。次要结局限于对分数各向异性、轴向扩散率、径向扩散率和平均扩散率在五个预定义感兴趣区域（ROI）的分析。对于这五个ROI内显著的时间点和治疗组相互作用，我们探究了WM纵向变化与认知功能/临床症状之间的关联。最后，我们探究了认知康复对WM的剂量反应效应。
共纳入111名UHR个体。失访率为26%。认知康复组平均完成了12小时的神经认知训练，远低于方案规定。与常规治疗相比，我们发现认知康复对全脑FA没有影响。次要ROI分析显示，左侧内侧丘系中AD的时间点*治疗之间存在名义上的显著相互作用（P = 0.016），但在多重比较校正后未保持显著。探索性检验表明，认知康复组中AD的这种变化与心理灵活性的改善相关（p = 0.001）。我们未发现神经认知训练对WM有剂量反应效应。
平均包含12小时神经认知训练的认知康复未改善UHR个体的整体或局部WM组织。有必要进一步研究认知训练的持续时间和强度，作为基于神经可塑性变化的必要前提条件。
ClinicalTrials.gov，标识符NCT02098408。
