Department of Psychiatric Research, Diakonhjemmet Hospital, Forskningsveien 7, 0373, Oslo, Norway.
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Sci Rep. 2024 Oct 1;14(1):22755. doi: 10.1038/s41598-024-73322-x.
The caudate nucleus is a part of the striatum, and striatal hyperdopaminergia is considered central to the pathophysiology of schizophrenia. How caudate volume is affected in schizophrenia and what role antipsychotics play remains unclear. In early-onset schizophrenia (EOS), where psychosis emerges during a neurodevelopmentally critical phase, the caudate may exhibit a heightened vulnerability to the effects of antipsychotic medications. We hypothesized effects of both antipsychotic medication use and age of onset on caudate in schizophrenia. We included adult patients with EOS (n = 83) and adult-onset schizophrenia (AOS) (n = 246), adult healthy controls (HC, n = 774), adolescent patients with non-affective psychosis (n = 56) and adolescent HC (n = 97). We obtained T1-weighted MRI scans using a 1.5T Siemens scanner and General Electric 3T scanners. In our main analysis, we tested for main and interaction effects of diagnosis and current antipsychotic medication use on caudate volume. Adult patients with EOS (p < 0.001) and AOS (p = 0.002) had both larger caudate than HC. Age of onset (EOS/AOS) interacted with antipsychotic use (p = 0.004) which was associated with larger caudate in EOS (p < 0.001) but not in AOS (p = 0.654). Conversely, among medicated patients only, EOS had larger caudate than AOS (p < 0.001). No other subcortical structures showed differences between medicated EOS and AOS. Medicated adolescent patients with non-affective psychosis and medicated adult patients with EOS showed similar caudate volumes. The results may indicate a schizophrenia-related and a medication-induced caudate increase, the latter restricted to patients with EOS and possibly occurring already in adolescence shortly after disease onset.
尾状核是纹状体的一部分，纹状体多巴胺能亢进被认为是精神分裂症病理生理学的核心。精神分裂症患者的尾状核体积如何受到影响，以及抗精神病药物起什么作用，目前仍不清楚。在发病早期（EOS），精神病出现在神经发育的关键阶段，尾状核可能对抗精神病药物的作用更为敏感。我们假设抗精神病药物的使用和发病年龄都会对精神分裂症患者的尾状核产生影响。我们纳入了成年 EOS 患者（n=83）、成年发病精神分裂症患者（AOS，n=246）、成年健康对照者（HC，n=774）、青少年非情感性精神病患者（n=56）和青少年 HC（n=97）。我们使用 1.5T 西门子扫描仪和通用电气 3T 扫描仪采集 T1 加权 MRI 扫描。在我们的主要分析中，我们检测了诊断和当前抗精神病药物使用对尾状核体积的主要和交互影响。EOS （p<0.001）和 AOS （p=0.002）成年患者的尾状核均大于 HC。发病年龄（EOS/AOS）与抗精神病药物的使用相互作用（p=0.004），这与 EOS 患者的尾状核增大有关（p<0.001），但与 AOS 患者无关（p=0.654）。相反，在用药患者中，EOS 的尾状核大于 AOS（p<0.001）。其他皮质下结构在用药的 EOS 和 AOS 之间没有差异。用药的青少年非情感性精神病患者和用药的 EOS 成年患者的尾状核体积相似。这些结果可能表明存在与精神分裂症相关的和由药物引起的尾状核增大，后者仅发生在 EOS 患者中，并且可能在疾病发病后不久的青少年期就已经发生。
