Functional Connectivity in Antipsychotic-Treated and Antipsychotic-Naive Patients With First-Episode Psychosis and Low Risk of Self-harm or Aggression: A Secondary Analysis of a Randomized Clinical Trial.
Functional Connectivity in Antipsychotic-Treated and Antipsychotic-Naive Patients With First-Episode Psychosis and Low Risk of Self-harm or Aggression: A Secondary Analysis of a Randomized Clinical Trial.
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抗精神病药物治疗和抗精神病药物初治首发精神病患者的功能连接性和自我伤害或攻击的低风险：一项随机临床试验的次要分析。
DOI：
10.1001/jamapsychiatry.2021.1422
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发表时间：
2021-09-01
期刊：
影响因子：
25.8
通讯作者：
Fornito A
中科院分区：
文献类型：
--
作者：
Chopra S;Francey SM;O'Donoghue B;Sabaroedin K;Arnatkeviciute A;Cropley V;Nelson B;Graham J;Baldwin L;Tahtalian S;Yuen HP;Allott K;Alvarez-Jimenez M;Harrigan S;Pantelis C;Wood SJ;McGorry P;Fornito A
抗精神病药物治疗和抗精神病药物初治的精神病患者是否存在不同的大脑连接模式，这些模式如何随时间演变？在一项在抗精神病药物初治患者中进行的三盲、纵向、安慰剂对照、随机化临床试验的次要分析中，患者在基线时相对于健康对照显示出广泛的脑连接障碍。接受治疗和安慰剂或治疗和抗精神病药物治疗的患者显示出随时间推移的回路特异性和治疗特异性连接正常化的证据。在这项研究中，首次发作精神病的一些突出的基线连接性差异在病程早期通过心理社会治疗和安慰剂进行了正常化，抗精神病药物发挥了回路特异性作用。这项随机临床试验的二次分析研究了抗精神病药物治疗和抗精神病药物初治精神病患者大脑连接的差异模式，以及这些模式如何随时间变化。功能连接改变（FC）是精神病患者静息态功能磁共振成像（rs-fMRI）研究中的常见发现，但FC紊乱在疾病早期如何演变，以及抗精神病药物治疗如何影响这些紊乱，仍然未知。研究首次发作精神病（FEP）的抗精神病药物初治和抗精神病药物治疗患者的纵向FC变化。这项三盲随机临床试验的次要分析在2008年4月至2016年12月的5年招募期内进行，其中59例抗精神病药物初治的FEP患者在6个月的治疗期内接受第二代抗精神病药物或安慰剂。参与者被要求具有较低的自杀倾向和攻击性，患有未经治疗的精神病的持续时间少于6个月，并且生活在有社会支持的稳定住所。两个FEP组都接受了强化的心理社会治疗。还招募了健康对照组。参与者在基线、3个月和12个月时完成了rs-fMRI扫描。数据分析时间为二零一九年五月至二零二零年八月。采用静息态功能MRI检测脑FC。患者接受第二代抗精神病药或匹配的安慰剂片剂。两组患者均接受了手动的心理社会干预。该分析的主要结局是研究（1）基线时患者和对照组之间的FC差异;（2）基线和3个月之间用药和未用药患者的FC变化;（3）纵向FC变化与临床结局之间的相关性。另一个目的是研究基线后12个月的长期FC变化。这些结果没有预先登记。分析了59例患者的数据（抗精神病药物加心理社会治疗：28 [47.5%];平均[SD]年龄，19.5 [3.0]岁; 15例男性[53.6%];安慰剂加心理社会治疗：31 [52.5%];平均[SD]年龄，18.8 [2.7]岁; 16名男性[51.6%]）和27名对照个体（平均[SD]年龄，21.9 [1.9]岁）。在基线时，与对照组相比，患者表现出广泛的功能性连接障碍，减少主要影响默认模式网络，边缘系统和大脑其余部分之间的相互作用。从基线到3个月，接受安慰剂的患者主要在相同的系统内表现出FC增加;其中一些变化与临床结局改善相关（典型相关分析R = 0.901;家族误差校正P = 0.005）。抗精神病药物暴露与主要在丘脑和大脑其余部分之间的FC增加相关。在这项临床试验的次要分析中，未接受过抗精神病药物治疗的FEP患者在基线时表现出广泛的功能性连接障碍，随后接受安慰剂和心理干预的患者出现默认模式网络和皮质边缘功能障碍的早期正常化。抗精神病药物暴露与集中在丘脑皮质网络的FC变化相关。 ACTRN12607000608460
Are there different patterns of brain connectivity in antipsychotic-treated and antipsychotic-naive patients with psychosis, and how do these patterns evolve over time? In this secondary analysis of a triple-blind, longitudinal, placebo-controlled, randomized clinical trial in antipsychotic-naive patients, patients showed widespread brain dysconnectivity at baseline relative to healthy controls. Patients treated with therapy and placebo or with therapy and antipsychotics showed evidence of circuit-specific and treatment-specific normalization of connectivity over time. In this study, some prominent baseline connectivity differences in first-episode psychosis normalized with both psychosocial therapy and placebo early in the illness course, with antipsychotics exerting circuit-specific effects. This secondary analysis of a randomized clinical trial investigates differential patterns of brain connectivity in antipsychotic-treated and antipsychotic-naive patients with psychosis and how these patterns change over time. Altered functional connectivity (FC) is a common finding in resting-state functional magnetic resonance imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotic treatment influences these disturbances, remains unknown. To investigate longitudinal FC changes in antipsychotic-naive and antipsychotic-treated patients with first-episode psychosis (FEP). This secondary analysis of a triple-blind, randomized clinical trial was conducted over a 5-year recruitment period between April 2008 and December 2016 with 59 antipsychotic-naive patients with FEP receiving either a second-generation antipsychotic or a placebo pill over a treatment period of 6 months. Participants were required to have low suicidality and aggression, to have a duration of untreated psychosis of less than 6 months, and to be living in stable accommodations with social support. Both FEP groups received intensive psychosocial therapy. A healthy control group was also recruited. Participants completed rs-fMRI scans at baseline, 3 months, and 12 months. Data were analyzed from May 2019 to August 2020. Resting-state functional MRI was used to probe brain FC. Patients received either a second-generation antipsychotic or a matched placebo tablet. Both patient groups received a manualized psychosocial intervention. The primary outcomes of this analysis were to investigate (1) FC differences between patients and controls at baseline; (2) FC changes in medicated and unmedicated patients between baseline and 3 months; and (3) associations between longitudinal FC changes and clinical outcomes. An additional aim was to investigate long-term FC changes at 12 months after baseline. These outcomes were not preregistered. Data were analyzed for 59 patients (antipsychotic medication plus psychosocial treatment: 28 [47.5%]; mean [SD] age, 19.5 [3.0] years; 15 men [53.6%]; placebo plus psychosocial treatment: 31 [52.5%]; mean [SD] age, 18.8 [2.7]; 16 men [51.6%]) and 27 control individuals (mean [SD] age, 21.9 [1.9] years). At baseline, patients showed widespread functional dysconnectivity compared with controls, with reductions predominantly affecting interactions between the default mode network, limbic systems, and the rest of the brain. From baseline to 3 months, patients receiving placebo showed increased FC principally within the same systems; some of these changes correlated with improved clinical outcomes (canonical correlation analysis R = 0.901; familywise error–corrected P = .005). Antipsychotic exposure was associated with increased FC primarily between the thalamus and the rest of the brain. In this secondary analysis of a clinical trial, antipsychotic-naive patients with FEP showed widespread functional dysconnectivity at baseline, followed by an early normalization of default mode network and cortical limbic dysfunction in patients receiving placebo and psychosocial intervention. Antipsychotic exposure was associated with FC changes concentrated on thalamocortical networks. ACTRN12607000608460
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影响因子：
4.5
作者：
Heckers, Stephan;Konradi, Christine
通讯作者：
Konradi, Christine
DOI：
10.1073/pnas.1820780116
发表时间：
2019-04-30
影响因子：
11.1
作者：
Baker, Justin T.;Dillon, Daniel G.;Holmes, Avram J.
通讯作者：
Holmes, Avram J.
影响因子：
6.6
作者：
Blessing, Esther M.;Murty, Vishnu P.;Goff, Donald C.
通讯作者：
Goff, Donald C.
影响因子：
7.6
作者：
Avram, Mihai;Brandl, Felix;Sorg, Christian
通讯作者：
Sorg, Christian
影响因子：
5.7
作者：
Alberton BAV;Nichols TE;Gamba HR;Winkler AM
通讯作者：
Winkler AM